A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors (NCT05572684), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0.

2. Clinical Question

3. Trial Design

This was a Phase 1b/2, open-label, non-randomized study of NC410 plus pembrolizumab. The registry describes a single-group design and lists enrollment as 97. Although the safety results are organized into four NC410 dose groups, that organization does not make the groups randomized comparison arms. Allocation is recorded as not applicable, and there is no like-for-like control group in the registry record.

All participants were described as receiving NC410 and pembrolizumab intravenously according to a treatment schedule, continuing until a reason for discontinuation was reached. The dose-group labels in the safety record are NC410 30mg, 60mg, 100mg, and 200mg, each with pembrolizumab. The registry does not report the dose-escalation procedure, the rationale for dose selection, the exact treatment schedule, or the rules used to assign participants to dose groups.

The study population was described as participants with advanced unresectable and/or metastatic solid tumors that were either immune checkpoint inhibitor-refractory or, for microsatellite-stable or microsatellite-instability-low tumors, immune checkpoint inhibitor-naïve. The condition list also names other tumor types and microsatellite-instability-high disease, but additional eligibility details are not reported in the registry record.

The study start is listed as 2022-10-06, and primary completion as 2025-04-30. Its current status is terminated. The reason for termination, the timing of that decision, and whether termination affected follow-up or outcome collection are not reported in the registry record. Open-label means treatment assignment was not masked; the record does not describe blinded outcome assessment.

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: Phase 1b (Dose Escalation) consisted of 4 planned cohorts evaluating NC410 IV doses ranging from 30 mg to 200 mg in combination with 400 mg pembrolizumab. A total of 97 participants were enrolled in Phase 1b between 06Oct2022 and 30Apr2023. Following completion of the Phase 1b portion, the sponsor decided not to initiate the planned Phase 2 portion of the study. No participants were enrolled in Phase 2.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set (SAS) will include all the subjects who receive any amount of study drug.

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 Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0, measured over From enrollment through up to 90 days after end of treatment, an average of 1 year.

The primary endpoint counts participants with treatment-emergent adverse events assessed using CTCAE v5.0. A participant count answers how many people in the defined safety population experienced an event; it is not a count of every event episode. The safety analysis set includes all participants who received any amount of study drug. The stated period for observing the outcome is from enrollment through up to 90 days after the end of treatment, with an average duration of 1 year.

In general, safety endpoints are used to describe the types and frequency of harms observed during treatment and follow-up. A count of affected participants can be useful for identifying safety patterns that warrant attention, but by itself it does not establish the cause of an event. Events may arise from disease, treatment, or other circumstances, and attribution requires information beyond a simple count. The registry record does not report an event-level breakdown for the primary endpoint or provide a causal assessment for each event.

The record also lists secondary outcomes covering tumor response, duration of response, disease control, progression-free survival, overall survival, and NC410 pharmacokinetics. Their numerical results and analysis details are not reported in the registry record, so the primary safety outcome cannot be used as a substitute for evidence about those other questions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help frame these results, but the registry record does not report a detailed statistical analysis plan. The posted information supports a descriptive reading of participant counts by dose group. It does not support an adjusted comparison or a causal estimate of treatment effect.

What does a participant count represent?

The primary outcome is a count of participants with treatment-emergent adverse events. In general, a participant-level count records whether a person experienced an event during the defined observation period. It differs from an event count, which could count multiple episodes in the same person. It also differs from an event rate, which relates events to time at risk. The registry does not report person-time estimates or repeated-event analyses, so the posted counts should not be interpreted as rates.

The safety analysis set includes participants who received any amount of study drug. This is a treatment-exposed population definition. In general, defining a safety population by exposure is useful for describing events among people who started treatment, but the resulting summaries do not necessarily describe everyone enrolled. The number enrolled is listed as 97, while the record does not provide a reconciliation between enrollment and the safety group counts or explain any exclusions from the safety population.

Why does the design matter?

Randomization is used in comparative trials to reduce systematic differences between treatment groups. This study is recorded as non-randomized and single-group, with no control group. The four dose-group summaries are therefore not equivalent to randomized arms. In general, a difference in observed counts across non-randomized groups may arise from differences in participant characteristics, disease severity, treatment exposure, follow-up, or other factors. Without details on allocation and adjustment methods, a difference cannot be attributed to dose.

Open-label means that masking was absent. In general, knowledge of treatment can influence reporting, clinical decisions, or the assessment of some outcomes. The registry does not report whether independent or blinded review was used for adverse events or other endpoints. It also does not report the criteria used to decide whether an event was treatment-emergent beyond naming the outcome and assessment scale.

How should uncertainty be understood?

In general, a confidence interval describes the range of estimates compatible with the observed data under a statistical model. It communicates precision as well as the direction and scale of an estimate. The registry entries do not include confidence intervals for the safety counts, and no inferential analysis is reported in the registry record. The counts alone do not show how uncertain an underlying event frequency may be, particularly in groups with limited numbers of participants.

In general, small groups can produce unstable estimates: each participant’s outcome has a substantial influence on the summary. This is relevant when interpreting the 30mg and 60mg group counts, which are reported with comparatively small denominators. It does not justify ranking the doses by apparent safety, because group membership was not randomized and the record does not establish comparable follow-up or participant profiles.

What do the planning assumptions mean?

In general, sample-size planning asks how much information a future study would need to detect a specified effect under stated assumptions. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also describes planning around fractions of an observed effect. These are planning assumptions, not evidence that the trial used that design or achieved a particular probability of detecting an effect. Planning illustrations are not observed power. The registry does not report the trial’s own sample-size justification or a protocol-based statistical plan, and the displayed assumptions do not turn this non-randomized study into a two-arm randomized comparison.

In general, over-dispersion occurs when variability in the data exceeds what a model assumes. Accounting for it can affect standard errors and intervals in count analyses. The record does not report a model for over-dispersion or any count-model analysis; moreover, the primary endpoint is described as a participant count rather than an event-frequency rate. No such model should be presumed.

The registry lists tumor response, survival, and pharmacokinetic outcomes in addition to safety. Analyses of these outcomes may require methods suited to binary response, time-to-event data, or concentration measurements. The endpoint definitions, censoring rules, analysis populations, and numerical results for those outcomes are not reported in the registry record. Their methods and results cannot be inferred from the safety counts.

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("NC410 30mg and Pembrolizumab", "60mg of NC410 and Pembrolizumab", "100mg of NC410 and Pembrolizumab", "200mg of NC410 and Pembrolizumab")
n      <- c(3, 11, 65, 18)
events <- c(3, 11, 62, 18)
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  NC410 30mg and Pembrolizumab  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  60mg of NC410 and Pembrolizumab  11  11  100.0  71.5  100.0  74.1  100.0  73.5  99.8
ARM  100mg of NC410 and Pembrolizumab  65  62  95.4  87.1  99.0  87.3  98.4  87.3  98.3
ARM  200mg of NC410 and Pembrolizumab  18  18  100.0  81.5  100.0  82.4  100.0  82.4  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including objective response rate, duration of response, disease control rate, progression-free survival, overall survival, and NC410 pharmacokinetic measures. When a study tests multiple outcomes, the chance of finding at least one apparently notable result can increase if no multiplicity strategy is used. In general, a statistical plan may address this through a testing hierarchy, adjusted significance thresholds, or a clear distinction between confirmatory and exploratory analyses. The approach used in this study is not reported in the registry record.

The record reports zero analyses and does not provide numerical results or inferential estimates for the listed secondary outcomes. It also does not report prespecified hypotheses, confidence intervals, p-values, or a hierarchy among endpoints. Consequently, no conclusion about statistical significance or multiplicity-adjusted evidence can be drawn from the posted information.

Missing-data methods are not reported in the registry record. The record does not explain how unavailable assessments, withdrawal, treatment discontinuation, or incomplete follow-up were handled for the safety endpoint or secondary outcomes. In general, missingness can affect estimates when participants with incomplete observations differ from those with complete data. The registry’s stated safety observation period does not itself specify an analytic rule for missing observations.

The safety analysis set is defined as participants receiving any amount of study drug. Other analysis populations for efficacy or pharmacokinetic outcomes are not reported in the registry record. The relationship between the listed enrollment and the participants included in each outcome analysis is also not described. These omissions limit assessment of whether the analyzed populations match the intended populations for each outcome.

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: mental status changes (33.3%), abdominal pain (18.2%), disease progression (18.2%), blood bilirubin increased (18.2%), small intestinal obstruction (9.1%).

The serious adverse-event figures are participant counts within each recorded dose group. The 30mg group lists 1 participant with a serious event among 3 at risk; the 60mg group lists 7 among 11; the 100mg group lists 25 among 65; and the 200mg group lists 4 among 18. These counts do not identify how many distinct event episodes occurred, and they do not provide person-time rates.

The registry also lists other adverse events as 3 of 3, 11 of 11, 62 of 65, and 18 of 18 across those respective groups. The serious and other-event categories should be read according to the record’s labels; the record does not give enough detail to establish whether or how the categories overlap. It does not provide a detailed definition of serious events, event-level listings, severity grades, or treatment-relatedness assessments.

Deaths are listed separately by group, but their causes and attribution are not reported in the registry record. The listed serious-event terms and percentages also lack an explained denominator. These summaries are descriptive safety information, not evidence that treatment caused a particular event or that one dose group is safer than another. Non-randomized allocation and unreported differences in exposure and follow-up prevent a fair causal comparison.

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

The registry record describes an open-label study of NC410 combined with pembrolizumab in participants with advanced unresectable and/or metastatic solid tumors. Its posted safety information gives participant counts for serious and other adverse events across NC410 dose groups. Those counts are useful for describing what was recorded among treated participants, and the listed serious-event terms provide additional descriptive context.

The results do not establish that the combination caused the reported events. A temporal event during treatment is not, by itself, proof of causation. The record does not provide event-level treatment attribution, detailed clinical context, or a comparison with an untreated or alternative-treatment group. Deaths are reported by dose group, but their causes and relationship to study treatment are not reported.

The dose groups cannot be interpreted as a controlled comparison. The design is described as non-randomized and single-group, and the registry explicitly does not treat the groups as like-for-like controls. Differences in participant characteristics, disease, treatment exposure, and follow-up could influence the observed counts. The available record does not report adjustment methods that would address such differences.

The safety counts also do not answer whether the combination improved tumor response, delayed progression, or affected survival. Those outcomes appear in the registry’s list of secondary endpoints, but their numerical results and analyses are not reported in the registry record. Likewise, the safety summaries do not establish a dose-response relationship or identify a preferred dose.

The appropriate reading is therefore narrow: the record reports adverse-event and death counts in the study’s dose groups, within a stated safety observation period. It does not support a causal treatment claim, a comparative safety conclusion, or an efficacy conclusion. Further interpretation would require details that are not reported in the registry record, including event attribution, participant characteristics, follow-up, and endpoint-specific analyses.

14. Why This Trial Matters Statistically

This study raises statistical issues common to early-phase research in heterogeneous solid tumors. Its stated population includes participants whose tumors were refractory to immune checkpoint inhibitors, as well as immune checkpoint inhibitor-naïve participants with specified microsatellite status. Combining differing clinical settings can make an overall summary harder to interpret: event counts reflect the population enrolled and do not necessarily apply equally to each disease or eligibility group. The registry record does not provide subgroup results that would clarify this.

The design also matters. The study is open-label and non-randomized, while safety summaries are divided by dose. In general, dose-group data can describe what happened during treatment, but they do not alone estimate the causal effect of increasing dose. Without randomization or reported adjustment, the observed groups may differ in ways that influence adverse events. This distinction is especially important when readers might be tempted to treat dose groups as comparative arms.

Another statistical consideration is the gap between an outcome being listed and its analysis being available. The registry names response, survival, and pharmacokinetic endpoints, but analyses and numerical results for them are not reported in the registry record. Endpoint labels indicate what the study intended to assess; they do not establish that an outcome was measured completely or demonstrate a result.

Finally, participant counts need context. Group sizes differ, the safety population is defined by treatment exposure, and individual follow-up is not reported. In general, the precision of a frequency estimate depends on the amount of information and the observation process. Descriptive counts should therefore be presented with care, without treating them as precise comparative estimates or as proof of treatment causation.

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 explain why the study was terminated. It also does not report whether termination changed the planned follow-up, the number of outcome assessments, or the timing of analyses. The listed primary completion date and current status provide study-level context but do not explain the completeness of the posted results.

The study had no randomized control group, and its dose groups are not like-for-like comparison arms. Details about dose assignment, participant characteristics by group, and adjustment for baseline differences are not reported in the registry record. This limits comparisons across doses and makes causal attribution especially uncertain.

The safety information lacks event-level detail, including the timing, duration, severity, and treatment-relatedness of events. The denominator behind the listed serious-event percentages is not explained. The record does not provide participant-level follow-up or person-time, so the counts cannot be interpreted as time-adjusted rates. The relation between the enrolled population and each outcome analysis is also not reported.

Although response, survival, and pharmacokinetic outcomes are listed, their numerical results and analysis methods are not reported in the registry record. Statistical methods for missing data, multiplicity, censoring, subgroup analysis, and uncertainty intervals are not reported either. These gaps limit both efficacy interpretation and assessment of the precision of the safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors — NCT05572684.
• Registry record last updated 2026-08-13; status last verified 2026-07.
• Results first posted 2026-08-13.
• 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

NCT05572684 is a Phase 1b/2, open-label, non-randomized study of intravenous NC410 plus pembrolizumab in advanced unresectable and/or metastatic solid tumors. The registry lists enrollment as 97 and identifies NC410 dose groups of 30mg, 60mg, 100mg, and 200mg. Its status is terminated; the reason is not reported in the registry record.

The primary outcome counts participants with treatment-emergent adverse events assessed using CTCAE v5.0. The posted safety information includes serious and other adverse-event counts, deaths, and selected serious-event terms. The record also lists tumor-response, survival, and pharmacokinetic outcomes, but their numerical results and analyses are not reported in the registry record. Because the study has no randomized control group, dose-group counts are descriptive and do not establish causal or comparative effects.