Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy (NCT05630937), a na phase 1, phase 2 study. The primary outcome is Phase I Drug Related Dose Limiting Toxicities (DLTs).

2. Clinical Question

The study asked whether NMS-01940153E could be administered to adults with unresectable hepatocellular carcinoma who had previously received systemic therapy, and what antitumor activity might be observed. It was a Phase I/II study of the drug as a single agent. The registry record describes safety, tolerability, and antitumor activity as the aims; it does not report an efficacy result.

The registry lists enrollment of 31 and a terminated status. That enrollment figure does not establish how many participants contributed to each outcome. The record gives evaluable-set details for the Phase I DLT endpoint and adverse-event counts by dose group, but does not report the primary DLT count itself. It therefore permits a description of the design and selected safety observations, not an estimate of treatment effect versus another therapy or no treatment.

3. Trial Design

This was a Phase I/II, open-label, non-randomized, multicenter study. The registry lists the study model as sequential and the allocation as not applicable. Its listed phases are Phase I and Phase II. The record gives a start date of 2020-11-13, a primary completion date of 2024-01-31, enrollment of 31, and a terminated status. A reason for termination is not reported in the registry record.

In Phase I, participants entered sequential cohorts at progressively higher dose levels, with dose escalation guided by dose-limiting toxicities. The stated aim was to identify a maximum tolerated dose based on DLTs observed in the first treatment cycle. The primary endpoint description identifies two explored dose levels: 100 mg/m2/week and 135 mg/m2/week. It states that all 12 Phase I treated participants were evaluable for DLT, with 6 treated at each dose level.

In Phase II, participants were to receive the recommended Phase II dose defined in Phase I. The brief description says Phase II was designed as a two-stage study, with an interim analysis for futility and stopping criteria for unacceptable toxicity. These are features of the stated design; whether the interim analysis or stopping rules were implemented is not reported in the registry record. The recommended Phase II dose itself is not reported in the registry record.

There was no concurrent randomized comparator. The sequential dose groups were used within a dose-escalation study, rather than to make a controlled efficacy comparison. Differences between their observed adverse-event counts cannot therefore be interpreted as causal dose effects. The record describes 23 outcome measures and no analysis entries. It does not report the statistical analysis plan, sample-size justification, or details of any efficacy analysis.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Phase I treated participants

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 treated participants

6. Primary Endpoint

The registry lists the primary outcome as Phase I Drug Related Dose Limiting Toxicities (DLTs), measured over Phase I: From screening to end of first 28-day cycle (17 months).

The primary endpoint is the count of Phase I participants experiencing drug-related dose-limiting toxicities. The record defines the DLT evaluation period as screening through the end of the first 28-day cycle, and describes the endpoint population as Phase I treated participants. It states that all 12 Phase I treated participants were evaluable and that 6 were treated at each of the two explored dose levels, 100 mg/m2/week and 135 mg/m2/week.

A DLT endpoint is used in early-phase dose escalation to identify toxicities that constrain treatment dosing. In general, observing DLTs during a defined early treatment window can inform selection of a dose for further study. The study description says the maximum tolerated dose was to be based on DLTs observed in the first cycle, and that the Phase II dose would be defined during Phase I.

The registry record says participants who experienced DLTs are presented, but the actual DLT count by dose is not reported in the registry record. The endpoint description does not provide the specific DLT criteria or an estimate of uncertainty around the count. Consequently, the primary endpoint’s intended role can be explained, but the reported record does not establish what DLT frequency was observed or which dose was selected.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study used a sequential, non-randomized design. In general, a sequential dose-escalation design assigns participants to dose cohorts in order, with later dose decisions informed by earlier safety observations. This differs from random allocation: dose groups do not arise from a randomized comparison, and their outcome differences may reflect participant or time-related differences as well as dose. The record describes progressively higher dose levels in Phase I and identifies the two levels explored. It does not report the specific escalation algorithm or statistical decision rule.

What does the DLT count represent?

The primary endpoint is a count of participants with drug-related DLTs during the first 28-day cycle. A count is an absolute number of people meeting an endpoint definition, rather than a continuous measurement. Counts are useful in early-phase studies because a serious or dose-limiting event can inform whether a dose should be explored further. General interpretation depends on the endpoint definition, observation window, and population included. The registry record specifies the window and evaluable population description, but does not report the detailed DLT criteria or the observed count by dose.

The endpoint description states that participants had to receive at least 66% of the study drug during the first 28-day cycle and undergo a DLT assessment within the DLT window to be included in the evaluable set. It also says all 12 Phase I treated participants were evaluable. These eligibility details matter because an endpoint count applies to the defined analysis population, not automatically to every person enrolled. The record does not explain how participants who might not meet those conditions would otherwise be handled.

Why does the design matter for interpreting adverse events?

The study was open-label, so treatment assignment was not masked. It was also non-randomized, with no control group. In general, open-label assessment may be influenced by knowledge of treatment, while a non-randomized comparison can be affected by differences between groups. Neither design feature makes descriptive safety reporting unusable, but they limit causal comparisons. Counts from the Phase I dose cohorts and the Phase II group should be read as observations within those groups, not as evidence that one dose caused more or fewer events than another.

The adverse-event entries include numbers at risk and numbers affected for serious and other event categories. In general, an at-risk denominator gives context for a count, but does not by itself convey the event timing, duration, recurrent events, or a participant’s overall clinical course. The listed figures are participant counts; the record does not provide enough detail to reconstruct event-level data. The percentages attached to selected serious-event terms should be read as registry-reported values, without inferring additional denominators or overlap among events.

What is the role of confidence intervals and statistical tests?

In general, a confidence interval describes the range of estimates compatible with the observed data under a specified statistical method. It communicates precision, not certainty that an effect is clinically important or causal. A hypothesis test addresses compatibility with a null hypothesis under its assumptions; it does not replace effect estimates or study-design considerations. No confidence interval or test result for the primary endpoint is reported in the registry record. There are no analysis entries, so statistical significance and precision for DLTs or efficacy cannot be assessed from the record.

For count outcomes, general methods may account for the number of participants observed and the amount of observation time, depending on the endpoint. When data are more variable than a simple model expects, over-dispersion can make standard errors too small if it is ignored. The record does not report a model, an over-dispersion assessment, or any adjusted analysis. It would therefore be inappropriate to infer that a particular count model or variance correction was used.

The Phase II description says the design included two stages, an interim futility analysis, and stopping criteria for unacceptable toxicity. In general, staged designs can allow a study to stop when accumulating evidence makes further study less informative or unacceptable on safety grounds. Such designs require prespecified decision rules and careful interpretation of any interim analysis. Whether the planned interim analysis occurred, its decision criteria, and any resulting decision are not reported in the registry record.

The record also does not report the statistical analysis plan, sample-size justification, or methods for handling missing outcomes. This means the posted material cannot establish which statistical methods were prespecified or whether the reported outcome entries reflect all planned analyses. Any sample-size planning illustrations based on observed effects should be understood as planning calculations, not as observed power or evidence that the study had adequate power.

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("100 mg/m2/Week Dose (Phase I)", "135 mg/m2/Week Dose (Phase I)")
n      <- c(6, 6)
events <- c(0, 2)
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  100 mg/m2/Week Dose (Phase I)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  135 mg/m2/Week Dose (Phase I)  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures, including safety outcomes and pharmacokinetic measures. It does not report a multiplicity strategy for interpreting multiple outcomes. In general, examining many outcomes can increase the chance of at least one apparently unusual result when each is considered separately. A prespecified hierarchy, adjustment, or clearly exploratory interpretation can help readers understand such findings, but the approach used for this study is not reported in the registry record.

The study description identifies objective response rate as the Phase II measure of antitumor activity, with a two-stage design and an interim futility analysis. The record does not state whether that interim analysis occurred, which hypotheses or decision thresholds were used, or how interim and final results were handled statistically. The presence of a planned interim analysis alone does not establish that an adjustment or stopping decision was made.

For the Phase I DLT endpoint, the record states that all 12 treated participants were evaluable and describes the inclusion conditions for the evaluable set. It does not give the number excluded from that set, if any, or describe missing-data procedures for other outcomes. Missing-data handling for the Phase II activity endpoint and the other listed measures is not reported in the registry record.

The record’s 31 enrollment figure should not be treated as the denominator for every endpoint: the endpoint and adverse-event entries specify their own populations and group denominators. The analysis populations for outcomes beyond those explicitly described are not reported in the registry record. There are no analysis entries, and the record does not provide a statistical analysis plan or a reconciliation of participants across all outcome populations. These gaps limit assessment of completeness and of how multiple outcome results, if any, were selected for reporting.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (16.7%), neutropenia (16.7%), sepsis (16.7%), device related bacteraemia (16.7%), disease progression (11.1%).

The serious adverse-event entries are descriptive counts by study group. The registry lists 1 affected among 6 at Phase I: 100 mg/m2/Week, 2 among 6 at Phase I: 135 mg/m2/Week, and 5 among 18 at Phase II: 100 mg/m2/Week. The record also lists deaths of 5, 5, and 9 in those respective groups. These are reported counts; the registry record does not establish that the deaths were caused by study treatment.

Selected serious-event terms are listed with registry-reported percentages: anaemia, neutropenia, sepsis, and device related bacteraemia at 16.7%; disease progression at 11.1%; and pathological fracture at 5.6%. These terms may not represent mutually exclusive groups of participants, and the record does not specify overlap or event-level timing. They should not be added together or interpreted as a single overall event rate.

The serious-event entries are not a randomized comparison. The study had no like-for-like control arm, and group counts alone do not adjust for differences in follow-up or participant characteristics. The record also includes a separate other adverse-event category, but does not provide enough detail to characterize event duration, recurrence, or attribution. These figures describe recorded safety events; they do not on their own establish causation or comparative risk.

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

The registry record documents a Phase I/II investigation of NMS-01940153E in adults with unresectable hepatocellular carcinoma previously treated with systemic therapy. It describes a Phase I dose-escalation approach focused on drug-related DLTs during the first 28-day cycle and a planned Phase II assessment of antitumor activity using objective response rate. It also records adverse-event counts across Phase I dose groups and a Phase II group.

Those details do not establish how many Phase I participants experienced a DLT. Although the endpoint description says all 12 Phase I treated participants were evaluable, the DLT result itself is not reported in the registry record. The recommended Phase II dose and maximum tolerated dose are also not reported. The record describes the planned Phase II endpoint but does not report an objective response result, so it cannot support a conclusion about antitumor activity.

The serious adverse-event counts and selected event terms provide safety observations, but not a controlled comparison. The study was open-label and non-randomized, and the groups do not serve as like-for-like controls. The listed death counts do not establish cause or treatment relationship. Nor can the reported event terms alone establish whether an event was caused by the study drug.

The registry lists a terminated status, but does not report the reason. That status should not be treated as evidence of a particular safety or efficacy outcome. More broadly, the record does not provide the statistical analysis plan, analysis entries, missing-data methods, or a reported efficacy analysis. The posted information therefore characterizes aspects of study design and selected safety reporting, while leaving key outcome and analysis questions unresolved. It should not be read as evidence that NMS-01940153E is effective or ineffective.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a dose-finding objective and an efficacy comparison. Phase I was designed around sequential dose cohorts and DLT observation in a defined early treatment window. That design can guide dose selection, but it is not a randomized test of one dose against another. Phase II was described as a two-stage assessment of objective response, but its outcome is not reported in the registry record.

The record also illustrates why the endpoint population and denominator matter. The primary endpoint description identifies a DLT-evaluable set and gives inclusion conditions, while adverse-event entries use group-specific denominators. The enrollment figure is not interchangeable with those outcome-specific populations. Interpreting a count without its population definition can misstate what was actually assessed.

Safety counts are useful descriptive information, but they do not by themselves answer causal questions. Without randomization or a concurrent control, differences across dose or phase groups can reflect more than dose. Event attribution, timing, follow-up, and completeness also matter; several of these details are not reported in the registry record.

Finally, the record names a Phase II futility analysis and toxicity stopping criteria, yet does not report whether those procedures occurred or what decisions followed. This distinction between planned methods and reported analyses is important when assessing a trial. The study’s terminated status and listed outcomes do not fill those gaps. The record supports careful description of the design and selected adverse-event observations, but not a complete statistical assessment of the primary endpoint or antitumor activity.

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.

A central limitation is that the primary DLT endpoint result is not reported in the registry record. The record gives the evaluable population and the two Phase I dose levels, but not the number experiencing DLTs. It also does not report the maximum tolerated dose or recommended Phase II dose. This prevents interpretation of the main dose-finding outcome.

The efficacy outcome is similarly unavailable: objective response rate is named as the Phase II measure of antitumor activity, but no response result is reported. The registry record contains no analysis entries. It does not provide confidence intervals, statistical tests, a statistical analysis plan, or sample-size justification, so precision and analysis choices cannot be assessed.

The design was open-label and non-randomized, with no concurrent control group. This limits causal interpretation and precludes a controlled estimate of treatment effect from the groups described. The record does not report detailed DLT criteria, event-level timing, missing-data procedures, or how the planned interim analysis and stopping rules were implemented. It also does not report the reason the study was terminated.

Finally, selected serious adverse-event terms and group counts do not establish treatment attribution, event overlap, or comparable follow-up across groups. The death counts are reported without cause or treatment relationship in the available record. These limitations mean the available information is best read as a partial description of study conduct and safety reporting, rather than a complete account of clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy — NCT05630937.
• Registry record last updated 2025-06-19; status last verified 2025-06.
• Results first posted 2025-05-07.
• 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 describes a Phase I/II, open-label, non-randomized, multicenter study of NMS-01940153E as a single agent in adults with unresectable hepatocellular carcinoma previously treated with systemic therapy. Phase I used sequential dose cohorts and focused on drug-related DLTs during the first 28-day cycle. The record identifies 100 mg/m2/week and 135 mg/m2/week as the explored Phase I dose levels. Phase II was described as an assessment of objective response rate at a dose defined in Phase I.

The registry lists enrollment of 31, a start date of 2020-11-13, a primary completion date of 2024-01-31, and a terminated status. It describes 23 outcome measures and contains no analysis entries. The Phase I DLT count, Phase II response result, reason for termination, and statistical analysis plan are not reported in the registry record. Adverse-event counts and selected serious-event terms are reported descriptively and do not establish treatment causation or comparative effects.