Dose Evaluation of MK-1966 in Combination With SD-101 in Participants With Advanced Malignancies (MK-1966-001): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Evaluation of MK-1966 in Combination With SD-101 in Participants With Advanced Malignancies (MK-1966-001) (NCT02731742), a non-randomized phase 1 study. The primary outcome is Percentage of Participants With a Dose Limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

NCT02731742, titled “Dose Evaluation of MK-1966 in Combination With SD-101 in Participants With Advanced Malignancies,” was a phase 1/1b, non-randomized, open-label study with a parallel model. It evaluated MK-1966 together with SD-101 in participants with advanced malignancies. Because treatment allocation was not randomized and there was no control group, the dose groups do not form a randomized comparison.

The study was designed to begin with Part A, an evaluation of four dose combinations. The stated purpose was to determine the maximum tolerated dose or maximum administered dose by assessing dose-limiting toxicities. Parts B and C were planned expansion cohorts intended to confirm or refine the MTD/MAD. The registry description anticipated approximately 20 participants in each expansion cohort, but the study was terminated by the sponsor before enrollment into Part A concluded and before enrollment into either expansion cohort began.

The registry lists enrollment of 14 participants and records the study as terminated. The study start date was 2016-06-22, and the primary completion date was 2018-01-08. These dates describe the registered study timeline; they do not establish that the planned dose evaluation or expansion work was completed. The registry record does not report the reason for termination beyond stating that termination was by the sponsor.

The primary endpoint focused on DLTs during Cycle 1, with each cycle defined as 21 days. The registry record does not report the allocation process among dose combinations, the dose-escalation decision rules, or a detailed statistical analysis plan. Those aspects should not be inferred from the dose-group labels or the planned expansion design.

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: The study was terminated prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment. This results disclosure is for Part A only.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The DLT evaluable population consisted of all participants who completed study drug in Cycle 1 or discontinued study drug during Cycle 1 due to a DLT.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With a Dose Limiting Toxicity (DLT), measured over From time of first dose of study drug to the end of Cycle 1. Each cycle was 21 days. (Up to 21 days).

The primary endpoint was the percentage of participants with a dose-limiting toxicity during Cycle 1, from the first dose of study drug to the end of that cycle. The DLT-evaluable population was defined as participants who completed study drug in Cycle 1 or discontinued study drug during Cycle 1 due to a DLT. This population definition matters because the percentage is intended to describe DLT occurrence among participants considered evaluable for the early-cycle safety assessment, rather than automatically among everyone enrolled.

The endpoint included a range of toxicities, including severe non-hematologic or hematologic toxicities, febrile neutropenia, certain laboratory abnormalities, drug-related adverse events leading to discontinuation, and delays to Cycle 2 due to study-drug-related toxicity. Attribution was based on the Investigator’s assessment that an event was possibly, probably, or definitely related to MK-1966 or SD-101. The registry record gives detailed toxicity criteria, but does not report the number of participants meeting the DLT definition or the resulting percentage.

In general, an early-cycle DLT endpoint is used in dose evaluation to characterize treatment-limiting toxicity over a defined assessment period. It is not an efficacy endpoint and does not, by itself, summarize all safety outcomes over the full duration of treatment. The registry’s 80% confidence interval label indicates the planned form of uncertainty reporting for this endpoint; the actual estimate and interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a percentage and labels its dispersion as an 80% confidence interval. It does not report an analysis for this endpoint. The concepts below explain how these methods are generally used; they do not describe an analysis confirmed in the registry record.

What does a percentage endpoint represent?

General statistical explanation: For a binary outcome, each evaluable participant is classified according to whether the event occurred during the defined assessment period. The percentage describes the share of the analysis population classified with the event. Its interpretation depends on a clear event definition, a clear time window, and a clear denominator. In this trial, the event was a DLT during Cycle 1, and the registry defines the DLT-evaluable population. However, the number of DLT-evaluable participants and the observed percentage are not reported in the registry record.

A percentage is descriptive, not a guarantee that the same rate would be observed in another group or study. It also does not convey how uncertain the estimate is by itself. With few evaluable participants, each participant’s classification can have a substantial influence on the percentage. That general consideration is relevant to early-phase dose evaluation, but the registry does not provide the primary endpoint counts needed to quantify its impact in this study.

What does an 80% confidence interval mean?

General statistical explanation: A confidence interval gives a range of values compatible with an estimate under the assumptions of the method used. Its width reflects statistical uncertainty: a narrower interval indicates greater precision, while a wider interval indicates less precision. An 80% confidence interval is the level named in the registry for the primary endpoint. The registry record does not state the interval’s endpoints or the method used to calculate it, so its width and the assumptions behind it cannot be evaluated.

A confidence interval is not a substitute for the underlying event count and denominator. Readers need those quantities to understand how the percentage was formed and to judge the amount of information available. Neither the primary percentage nor the corresponding interval is reported in the registry record. The interval label alone does not establish that an interval was calculated or posted.

How should the dose groups be understood?

General statistical explanation: Randomization helps make treatment groups comparable, on average, with respect to factors that can affect outcomes. This study was non-randomized and open-label, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Consequently, descriptive differences between dose groups may reflect participant characteristics, the sequence of dose evaluation, chance, or other factors, as well as any dose-related differences. A causal interpretation would require a design and analysis that support it; none is reported in the registry record.

The parallel model describes the study’s group structure, but does not turn the groups into randomized comparators. The posted serious adverse event counts should therefore be read within each listed group, not as evidence from a controlled comparison. No comparative statistical estimates or tests are listed.

What can be concluded from the posted analysis information?

General statistical explanation: An analysis plan ordinarily specifies the outcome definitions, analysis populations, treatment of missing observations, estimation methods, and any planned hypothesis tests or multiplicity adjustments. The registry record defines the DLT-evaluable population and reports an 80% confidence interval label, but a detailed statistical plan is not reported in the registry record. The record lists no analyses, and it does not provide a primary endpoint estimate, confidence interval, or hypothesis test.

The record’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They do not describe the trial’s own design or establish observed power. Since the trial was non-randomized and the registry does not report comparative primary outcome results, those general planning assumptions cannot be used to infer a treatment effect or the precision of the posted safety counts.

In general, over-dispersion occurs when variation in outcomes is greater than a model expects; accounting for it can prevent overly narrow uncertainty estimates. The registry does not report a model for the primary endpoint or any over-dispersion assessment, so no such method should be attributed to this study. More broadly, the methods actually used for any unposted analysis are not reported in the registry record.

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("MK-1966 70 mg+SD-101 1 mg", "MK-1966 70 mg+SD-101 4 mg", "MK-1966 210 mg+SD-101 4 mg", "MK-1966 700 mg+SD-101 4 mg")
n      <- c(3, 3, 5, 2)
events <- c(0, 0, 1, 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  MK-1966 70 mg+SD-101 1 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  MK-1966 70 mg+SD-101 4 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  MK-1966 210 mg+SD-101 4 mg  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  MK-1966 700 mg+SD-101 4 mg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan for managing multiplicity across endpoints, dose combinations, or any interim looks. It also lists no analyses. This means the record does not establish which outcomes or comparisons, if any, were treated as confirmatory, or whether adjustments to account for multiple testing were planned or used. The absence of that information should not be filled in by assuming a conventional approach.

The primary endpoint’s stated analysis population was the DLT-evaluable population: participants who completed study drug in Cycle 1 or discontinued study drug during Cycle 1 due to a DLT. The record does not report how many participants met this definition or how participants with other reasons for not completing the assessment were handled. It does not describe imputation, censoring, or other missing-data procedures for the primary endpoint. The number and reasons for any missing primary outcome observations are not reported in the registry record.

The study’s termination before Part A enrollment concluded and before Parts B and C began also limits what can be inferred about planned analyses. The registry does not report whether any interim analysis was conducted, how dose decisions were made, or whether early termination changed the analysis plan. Those details are not reported in the registry record. The endpoint definition is available, but the analysis population actually used and the handling of incomplete observations cannot be verified from the posted record.

In general, multiplicity can increase the chance of a misleading result when many questions are tested without an appropriate strategy. Missing outcome information can also affect both the estimate and its uncertainty, depending on why observations are absent. These are general statistical concerns, not claims that a particular error occurred in this trial.

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: skin infection (50.0%), pyrexia (33.3%), pleural effusion (33.3%), urinary tract infection (16.7%), hyponatraemia (16.7%).

The registry reports serious adverse events by dose group. For MK-1966 70 mg+SD-101 1 mg, 1 participant was affected among 3 at risk; for MK-1966 70 mg+SD-101 4 mg, 1 was affected among 3 at risk; for MK-1966 210 mg+SD-101 4 mg, 3 were affected among 6 at risk; and for MK-1966 700 mg+SD-101 4 mg, 1 was affected among 2 at risk. These are descriptive counts, not adjusted estimates or randomized comparisons.

The registry separately lists other adverse events affecting 3, 3, 6, and 2 participants in those groups, respectively. Death counts are listed as 1, 2, 5, and 0, respectively. The record does not report whether these deaths were related to treatment or provide an analysis of their causes. Serious adverse event counts should not be equated with the primary DLT endpoint: a DLT had its own Cycle 1 definition and required an Investigator assessment of possible, probable, or definite relation to study drug.

The registry’s serious-event terms include Skin infection (50.0%), Pyrexia (33.3%), Pleural effusion (33.3%), Urinary tract infection (16.7%), Hyponatraemia (16.7%), and Hypotension (16.7%). The record does not provide enough context in this listing to interpret these terms as comparative risks across dose groups. Small, non-randomized groups and the early termination are important limits on interpretation.

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

The record establishes that a phase 1/1b study evaluated MK-1966 with SD-101 in advanced malignancies and defined a Cycle 1 DLT endpoint for dose evaluation. It also documents that the study was terminated before enrollment into Part A concluded and before either planned expansion cohort began. Serious adverse event counts and selected serious-event terms are posted by the registry.

Those details do not establish the primary endpoint result. The percentage of participants with a DLT, its denominator, and its 80% confidence interval are not reported in the registry record. The record therefore does not show which dose combination, if any, met the study’s stated goals for determining or refining an MTD/MAD. It also does not report an efficacy result. The endpoint described is a safety measure, not a measure of tumor response or clinical benefit.

The serious adverse event and death counts are descriptive. They do not determine whether an event was caused by study treatment, and the registry does not report a causal analysis. Nor do the dose groups provide a randomized basis for comparing safety: allocation was non-randomized, and the arms are not like-for-like controls. Differences in counts should not be interpreted as proof of a dose effect.

In general, a trial that stops before planned enrollment and expansion may leave its central questions unresolved, especially when outcome estimates and analysis details are not posted. This does not erase the design information or the reported event counts, but it limits how far those details can be taken. The available registry record supports a description of the study’s plan, early termination, and listed safety observations; it does not support a definitive conclusion about comparative safety, efficacy, or the selected dose.

14. Why This Trial Matters Statistically

This trial is statistically important because it illustrates the difference between a planned dose-evaluation study and a completed dose-evaluation result. The protocol description states that Part A was intended to use DLTs to determine the MTD/MAD and that Parts B and C were planned to confirm or refine it. Yet the registry records termination before Part A enrollment concluded and before expansion began. The planned design and the posted evidence are therefore not interchangeable.

It also highlights why analysis populations and outcome definitions matter. The DLT endpoint applies to a defined DLT-evaluable population and a defined Cycle 1 assessment period. A percentage without its numerator, denominator, and uncertainty would not be enough to judge the result; in this record, those primary outcome results are not reported at all. The registry’s confidence-interval label signals an intended form of precision reporting, but the interval itself is absent.

The trial also underscores the limits of interpreting safety counts across non-randomized groups. Dose-group counts can describe what was recorded in each group, but they do not provide a controlled comparison. Small group counts, early termination, and missing analysis details make causal interpretations particularly unsupported.

More generally, registry records can contain useful design and safety information while leaving major inferential questions unanswered. A careful statistical reading separates the design’s stated aims from completed analyses, distinguishes a DLT from other adverse event summaries, and treats unreported methods as unknown. That distinction is central to transparent interpretation of early-phase clinical research.

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 central limitation is that the registry record does not report the primary DLT outcome result, its denominator, or its 80% confidence interval. The stated primary endpoint can be understood from its definition, but its observed value and precision cannot be assessed. The registry lists no analyses, so no primary endpoint test or comparative estimate is available.

The study was non-randomized and open-label. The registry itself warns that the arms are not a like-for-like control comparison. Consequently, the serious adverse event counts by dose group cannot establish a causal dose effect. The record does not report treatment attribution for the listed deaths, and the selected serious-event terms do not supply a complete primary endpoint analysis.

Termination occurred before Part A enrollment concluded and before Parts B and C began. Thus, the planned expansion cohorts did not contribute results in the registry record, and the intended confirmation or refinement of the MTD/MAD is not documented as completed. The reason for sponsor termination is not reported in the registry record.

Further limitations include the absence of reported methods for missing data, multiplicity, interim analyses, and detailed statistical analysis. The DLT-evaluable population is defined, but the number analyzed and the handling of participants who did not meet that definition for other reasons are not reported. The registry’s planning assumptions do not resolve these gaps or substitute for an analysis of observed outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dose Evaluation of MK-1966 in Combination With SD-101 in Participants With Advanced Malignancies (MK-1966-001) — NCT02731742.
• Registry record last updated 2019-02-04; status last verified 2018-09.
• Results first posted 2019-02-04.
• 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

NCT02731742 was a phase 1/1b, non-randomized, open-label study of MK-1966 with SD-101 in advanced malignancies. The registry lists enrollment of 14 participants and a terminated status. The study was intended to evaluate four dose combinations in Part A and then proceed to expansion cohorts, but termination occurred before Part A enrollment concluded and before Parts B and C began.

The primary endpoint was the percentage of DLT-evaluable participants with a DLT during Cycle 1, with an 80% confidence interval identified for dispersion. The endpoint result and statistical analyses are not reported in the registry record. Serious adverse event counts, other adverse event counts, deaths, and selected serious-event terms are listed by dose group. These are descriptive observations from non-randomized groups, not controlled treatment comparisons.