A Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors (NCT04408599), a non-randomized 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 1/2, open-label, nonrandomized, sequential dose-escalation study of NC410. The registry record lists enrollment of 46 and describes participants with advanced or metastatic solid tumors, including ovarian cancer, gastric cancer, and colo-rectal cancer. The sponsor was NextCure, Inc. The record lists a start date of 2020-06-10, a primary completion date of 2023-07-06, and a status of terminated. The reason for termination is not reported in the registry record.

Participants entered dose cohorts for NC410 at 3mg, 6mg, 15mg, 30mg, 60mg, 100mg, or 200mg. Each dose was described as an intravenous infusion administered in 14 day dosing cycles. Sequential allocation means the cohorts were organized in sequence rather than assigned through randomization. The record does not report the precise rules used to move between dose levels, or whether changes to the escalation plan were made.

The study had no masking. Participants and study personnel were therefore not described as blinded to treatment assignment. There was no randomized comparator, and the registry record explicitly cautions that the arms are not a like-for-like control comparison. Cohort differences may reflect the sequence of enrollment and other differences between the groups, as well as dose. A direct causal comparison between doses is not justified by the design alone.

The primary outcome was the number of participants with treatment-emergent adverse events assessed by CTCAE v5.0. The Safety Analysis Set was defined as subjects who received any amount of study drug. Secondary outcomes included response, duration of response, disease control, progression-free survival, overall survival, and NC410 pharmacokinetic measures. The registry record does not report the statistical plan, sample-size justification, or the reason the study was terminated.

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 1a (Dose Escalation) consisted of 7 planned cohorts (NC410 IV doses 3mg to 200mg). Phase 1b (Safety Expansion) consisted of 3 cohorts (NC410 IV doses 30mg , 60mg and 100mg). Phase 1 enrolled 46 participants. NextCure decided to forgoe moving forward with NC10 as a monotherapy in Phase 2.

Only the first 6 of 7 groups are shown.

Overall Study

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.

Only the first 6 of 8 groups are shown.

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 by CTCAE v5.0. It is a participant-level count: the focus is whether a participant had an event, rather than the total number of event episodes. A participant can experience more than one event, so the number of participants with an event should not be read as a count of all events.

The registry specifies the Safety Analysis Set as subjects who received any amount of study drug. This population is relevant to a safety question because it includes people who were exposed to NC410, rather than all those who may have enrolled. The registry record does not provide the number in the Safety Analysis Set, so the enrolled number should not be treated as the endpoint denominator.

The observation period ran from enrollment through up to 90 days after the end of treatment, with an average of 1 year stated in the record. The period matters because adverse events can be counted only when they fall within the defined follow-up. Participants may have had different lengths of exposure or observation; the registry record does not describe how those differences were handled in the summaries.

Counting participants with adverse events is a useful way to describe the frequency of safety findings in an early-phase dose-escalation study. It is descriptive, however: by itself, it does not establish that NC410 caused an event, quantify an individual’s risk, or show how the findings compare with an untreated or randomized control group. The registry record does not report a formal comparative analysis of this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

The primary outcome is a count of participants with treatment-emergent adverse events. This differs from a count of event episodes. If one person experiences several events, a participant-level measure still counts that person once for the relevant outcome. The registry record also distinguishes serious adverse events from other adverse events in the safety summaries. The two kinds of counts should not be combined or treated as interchangeable.

The listed number at risk is the denominator associated with each cohort’s posted count. Comparing the affected count with the at-risk count is a way to understand the cohort summary, but those summaries do not account for differences in exposure duration or follow-up. No adjusted rate analysis is reported in the registry record. The record’s Safety Analysis Set definition also matters: it includes subjects who received any amount of study drug, and is not necessarily identical to everyone enrolled.

Why does the study design affect comparison?

In general, random assignment helps balance participant characteristics between treatment groups, on average. This study was nonrandomized and sequential, so that protection does not apply. Participants in one dose cohort may differ from those in another for reasons other than dose. The cohorts also entered in sequence, which means aspects of enrollment or study conduct could vary over time. The registry record provides no adjusted analysis to address such differences.

Open-label design means treatment was not masked. In general, knowledge of treatment can influence reporting, assessment, or decisions about follow-up. The registry record does not describe whether any outcome assessments were independently reviewed or whether safeguards against assessment bias were used. These omissions do not establish that bias occurred; they limit what can be concluded about its presence or absence.

What can inferential statistics add?

In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical model. A hypothesis test evaluates compatibility between observed data and a stated null model. Neither method removes design limitations, and neither turns a nonrandomized cohort comparison into a randomized one. The registry record does not report inferential analyses for the listed adverse-event counts, including confidence intervals or p-values.

In general, sparse counts can produce imprecise estimates, especially when cohort sizes are small. Standard methods may also rely on assumptions that are difficult to assess with limited data. An unadjusted calculation from summary counts, if presented, would not account for participant-level characteristics, differing exposure, or sequencing. No recalculated effect estimate or comparative test is reported in the registry record, so the counts should be read descriptively.

How should sequential dose escalation be understood?

Sequential dose escalation organizes participants into dose levels in a progression. This is not the same as random allocation across doses. A higher dose cohort may be enrolled after experience has accumulated at earlier doses, and the characteristics or circumstances of enrollment may differ. The registry record does not report the escalation rules, decision criteria, or a dose-response model. It is therefore not possible to infer from the design description alone how dose choices were made or what stopping criteria applied.

The listed intervention descriptions specify intravenous administration in 14 day dosing cycles. They do not, by themselves, establish how many cycles each participant received or the amount of time each participant remained at risk. In general, raw counts can be affected by different amounts of exposure and observation. The record does not report an exposure-adjusted safety analysis.

What do the planning assumptions mean?

In general, a sample-size calculation is a planning exercise that estimates how much information a future study might need under stated assumptions. It is not a result observed in the trial. The planning assumptions described for the posted illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. For time-to-event illustrations, the stated quantity is the total number of events; other illustrations refer to participants per arm.

Those assumptions are not a description of this study’s nonrandomized, sequential dose cohorts. The registry record does not report the trial’s own sample-size justification or statistical plan. A planning illustration based on an observed effect should not be interpreted as observed power, and it does not show that the trial was designed to detect that effect. The registry record also does not provide the statistical analyses needed to assess a dose comparison.

What is not available for statistical assessment?

The record lists nine outcome measures, including objective response rate, duration of response, disease control rate, progression-free survival, overall survival, maximum plasma concentration, area under the curve, and half-life. Their definitions identify questions the study intended to assess, but analyses and numerical results for these secondary measures are not reported in the registry record. The record does not report estimation methods, covariate adjustment, handling of censored observations, or uncertainty measures for them.

Thus, the statistical interpretation is constrained to the reported cohort-level safety summaries and design features. General statistical concepts can explain what additional analyses might address, but they cannot supply missing methods or results. Any stronger comparison would require details and participant-level information 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("NC410 3mg", "NC410 6mg", "NC410 15mg", "NC410 30mg", "NC410 60mg", "NC410 100mg")
n      <- c(3, 3, 4, 10, 10, 10)
events <- c(3, 3, 4, 9, 10, 9)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  NC410 3mg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  NC410 6mg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  NC410 15mg  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  NC410 30mg  10  9  90.0  55.5  99.7  59.6  98.2  58.7  97.7
ARM  NC410 60mg  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8
ARM  NC410 100mg  10  9  90.0  55.5  99.7  59.6  98.2  58.7  97.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists several secondary outcomes: objective response rate, duration of response, disease control rate, maximum plasma concentration, progression-free survival, overall survival, area under the curve, and half-life. It does not report a statistical analysis plan describing how these outcomes were prioritized or how multiple statistical tests, if any, were handled. In general, testing many outcomes can increase the chance of finding an apparently notable result by chance. Whether and how that issue was addressed is not reported in the registry record.

Outcome analyses for the listed secondary measures are not reported in the registry record. The record also does not describe missing-data rules, reasons for missing measurements, or methods for handling participants who discontinue treatment or have incomplete follow-up. For time-to-event outcomes, it does not report censoring rules or analysis methods. These details affect how estimates should be interpreted and whether participants with different follow-up contribute comparably.

The primary outcome population is defined as the Safety Analysis Set, including subjects who received any amount of study drug. The registry record does not report the size of this set or give further analysis-population definitions for the secondary outcomes. It is not possible to assume that every enrolled participant contributed to every measure.

In general, a clear analysis plan specifies populations, outcome definitions, missing-data handling, and any multiplicity approach before results are examined. The statistical plan and the trial’s sample-size justification are not reported in the registry record. Without those details, the posted counts can be described, but the prespecified status of particular analyses and the handling of incomplete data cannot be assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain upper (33.3%), ascites (33.3%), biliary obstruction (33.3%), arthralgia (33.3%), colorectal cancer (33.3%).

The safety summaries list, for each NC410 dose cohort, the number at risk and the number affected by serious adverse events and other adverse events. For serious events, the affected counts were 1 of 3 at 3mg, 3 of 3 at 6mg, 2 of 4 at 15mg, 5 of 10 at 30mg, 5 of 10 at 60mg, 7 of 10 at 100mg, and 3 of 6 at 200mg. For other adverse events, the counts were 3 of 3 at 3mg, 3 of 3 at 6mg, 4 of 4 at 15mg, 9 of 10 at 30mg, 10 of 10 at 60mg, 9 of 10 at 100mg, and 6 of 6 at 200mg.

These are participant counts within small, sequential cohorts. The same participant may have experienced more than one event, and the number affected does not indicate the total number of event episodes. The record’s time window extends from enrollment through up to 90 days after the end of treatment, with an average of 1 year stated. It does not give cohort-specific exposure or follow-up details, so the counts should not be read as exposure-adjusted rates.

The record lists deaths by cohort, but those counts alone do not establish cause or attribution. Serious adverse-event terms are also listed, each with a reported 33.3%; the record does not provide sufficient context to interpret those percentages as cohort-specific risks. None of these summaries supports a randomized comparison between doses.

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

The posted results provide a descriptive account of adverse events reported across the NC410 dose cohorts. They show how many participants were listed as affected by serious and other adverse events in each cohort, alongside the number at risk. They also list death counts and several serious adverse-event terms. These observations are relevant to understanding what was recorded during the study, but they are not, on their own, a complete statistical assessment of safety.

The study design sets important limits. It was nonrandomized, open-label, and sequential, and there was no randomized control group. The registry record cautions that the dose arms are not a like-for-like comparison. Differences between cohort counts therefore cannot be attributed to dose alone. The counts also do not establish causation for an individual event or death, and they do not show how the event burden would compare with a control condition.

The registry record lists response, disease-control, survival, and pharmacokinetic outcomes, but their numerical analyses are not reported in the registry record. As a result, the available information does not support an efficacy conclusion. The presence of a listed outcome measure should not be confused with a reported result, and no treatment benefit or lack of benefit can be inferred from the safety counts.

The enrollment entry is 46, but the primary safety population is defined separately as subjects who received any amount of study drug. The size of that analysis set is not reported in the registry record. Nor are the statistical analysis plan, missing-data rules, sample-size justification, or reason for termination reported. Those omissions limit assessment of completeness, precision, and prespecification.

The most defensible reading is therefore narrow: the record documents cohort-level safety counts in an early-phase dose-escalation study, while leaving substantial uncertainty about comparative safety and efficacy. The counts are observations, not proof of treatment effect, comparative risk, or causation.

14. Why This Trial Matters Statistically

Early-phase dose-escalation studies address questions that differ from those in randomized efficacy trials. Their sequential cohorts can describe safety observations at successive dose levels, but they do not inherently provide a fair comparison between doses. This study’s registry record makes that limitation explicit: allocation was nonrandomized and the arms are not a like-for-like control comparison. That design detail is central to interpreting every contrast between cohorts.

The endpoint also illustrates why statistical language matters. A count of participants with an event is not the same as a count of event episodes, and neither one is automatically an estimate of causally attributable harm. The distinction between the at-risk count, affected count, serious events, and other events helps prevent misreading the summaries. Small cohort counts are best treated as descriptive evidence, not precise rankings of doses.

The study’s listed secondary measures span tumor response, survival, and pharmacokinetics. Their inclusion indicates the range of questions the trial was intended to address, but listed outcomes without reported analyses cannot answer those questions. Separating intended measurement from reported results is an important statistical discipline, particularly when the primary outcome is safety-focused.

Finally, the record exposes key areas where statistical interpretation depends on fuller reporting: the analysis plan, population sizes, missing-data handling, follow-up, and rationale for study termination. These are not merely technical details. They determine how confidently results can be interpreted and compared. The record is useful as a description of design and posted safety observations, while leaving important inferential questions unresolved.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the reason the study was terminated. It also does not provide a detailed account of dose-escalation rules, cohort-entry decisions, or changes to the study procedures. Without those details, the rationale for the sequence of dose cohorts and any consequences for interpretation cannot be assessed.

Although enrollment is listed as 46, the size of the Safety Analysis Set is not reported. The primary analysis population includes subjects who received any amount of study drug, so enrollment cannot be assumed to equal the population contributing to the safety summaries. The record also does not provide individual-level exposure, duration of treatment, cohort-specific follow-up, or the number of participants with complete observations.

The safety results are presented as counts without reported uncertainty intervals or adjusted comparisons. The cohorts are nonrandomized and sequential, and the registry record warns against treating them as like-for-like controls. Participant characteristics, exposure, and observation time may differ between cohorts; the record does not report analyses addressing these possibilities. Counts of deaths do not identify cause or establish treatment attribution.

The record lists secondary response, survival, and pharmacokinetic outcomes but does not report their analyses or numerical results. It also does not report the statistical analysis plan, multiplicity procedures, sample-size justification, or missing-data methods. These gaps make it difficult to assess precision, the prespecified nature of analyses, or the potential effect of incomplete follow-up. The endpoint timeframe is stated as extending through up to 90 days after treatment, with an average of 1 year, but participant-level follow-up is not described.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors — NCT04408599.
• Registry record last updated 2024-07-25; status last verified 2024-07.
• Results first posted 2024-07-25.
• 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

The registry record describes a Phase 1/2, open-label, nonrandomized, sequential dose-escalation study of NC410 in advanced or metastatic solid tumors. It lists enrollment of 46, seven dose cohorts from 3mg through 200mg, and intravenous dosing in 14 day cycles. The listed primary outcome is the number of participants with treatment-emergent adverse events assessed by CTCAE v5.0 in a Safety Analysis Set of subjects who received any amount of study drug.

The record lists cohort-level serious and other adverse-event counts and deaths. It also names secondary response, survival, and pharmacokinetic measures, but analyses for those outcomes are not reported in the registry record. The study is listed as terminated, and the reason is not reported in the registry record. Because there was no randomized control group and the cohorts were sequential, the posted counts are descriptive and do not establish a causal or comparative treatment effect.