A Study of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma (NCT05653427), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment.

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label study of amivantamab monotherapy in participants with previously treated advanced hepatocellular carcinoma. The registry lists the study model as sequential, allocation as not applicable, and masking as none. It describes one amivantamab monotherapy group and no comparator arm. Consequently, the design can describe outcomes observed among participants receiving the study treatment, but it cannot provide a randomized comparison with another treatment or a control group.

The registry lists an enrollment of 18. This is the recorded enrollment figure; the registry record does not state in the registry record whether it represents a planned or actual enrollment count. The start date is 2022-12-08, and the primary completion date is 2023-10-10. The study status is terminated. The reason for termination is not reported in the registry record.

The arm description specifies intravenous amivantamab once weekly on Days 1 and 2 in Cycle 1, followed by administration on Days 1 and 15 from Cycle 2 onwards, with dosing based on body weight. Each cycle is 28 days. The adverse-event group is titled Amivantamab Monotherapy (1050/1400 mg), but additional information about dose selection or any changes to the schedule is not reported in the registry record.

The stated purpose was to characterize preliminary antitumor activity at the recommended dose in participants with previously systemically treated hepatocellular carcinoma. The primary endpoint was investigator-assessed objective response rate under RECIST version 1.1. Secondary outcomes included duration of response, disease control rate, progression-free survival, overall survival, adverse events, laboratory and vital-sign abnormalities, and maximum observed serum concentration. Numerical results for these outcomes are not reported in the registry record.

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 planned to be conducted in 3 parts: Part 1, main Part 2 and expansion Part 3. However, due to the early termination of study, the enrollment was discontinued before planned enrollment was achieved in Part 2. Due to changes in the planned analysis, efficacy and safety data were analyzed together for Part 1 and Part 2 and Part 3 was not conducted. As a result, combined results for both parts were presented.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Response evaluable analysis set included all participants who received at least 1 dose of study treatment; had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression/death prior to the first post-baseline disease assessment.

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 Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment, measured over From start of treatment on Day 1 up to 3.8 months.

The primary endpoint was objective response rate (ORR), defined as the percentage of participants with a confirmed complete response or partial response according to investigator assessment using RECIST version 1.1. Under the registry’s definition, complete response requires disappearance of extranodal lesions, regression of nodal lesions to less than 10 mm short axis, and normalization of tumor marker level. Partial response requires at least a 30% decrease in the sum of target-lesion diameters from baseline.

ORR is a binary outcome at the participant level: each participant either meets the response definition or does not. Reporting the percentage gives a direct description of how common confirmed tumor response was in the analyzed group. It is a measure of tumor shrinkage meeting specified criteria, rather than a direct measure of how long a response lasts or how long participants live. Those questions relate to other listed outcomes, including duration of response, progression-free survival, and overall survival.

The registry specifies a 95% confidence interval for the primary endpoint and a timeframe from the start of treatment on Day 1 up to 3.8 months. However, the numerical ORR and confidence interval are not reported in the registry record. The endpoint definition alone therefore does not establish how many participants responded or how precisely the response rate was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details below explain general concepts relevant to the outcomes described in the registry record. They are not a claim that the study used any particular method beyond what the record states.

What does the primary endpoint count?

ORR is a binary participant-level outcome. A participant is counted as having a response if investigator assessment identifies a confirmed complete response or partial response under RECIST version 1.1. The endpoint is expressed as a percentage of participants in the defined analysis set. The registry describes the response-evaluable analysis set as including participants who received at least 1 dose and had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression or death before the first post-baseline assessment. The record does not report how many participants met this analysis-set definition.

RECIST supplies operational criteria for classifying tumor response. In this study’s description, complete response involves disappearance or normalization findings, while partial response depends on a decrease in the sum of target-lesion diameters relative to baseline. Applying specified criteria can make assessments more consistent than relying on an informal impression of change. Investigator assessment is the method named in the registry; whether assessments were independently reviewed is not reported in the registry record.

What does a confidence interval communicate?

General explanation: a confidence interval expresses uncertainty around an estimated quantity. For a response percentage, the interval reflects that the estimate is based on a finite group of observed participants and may be sensitive to which participants enter the analysis set. A narrower interval generally indicates greater precision under the method used; a wider interval indicates greater uncertainty. It does not by itself show that a treatment caused an outcome, nor does it replace the need to examine the study design.

The registry specifies a 95% confidence interval for ORR, but its numerical limits are not reported in the registry record. Without the point estimate, interval limits, response count, and analyzed denominator, readers cannot assess the precision of the primary estimate from this record.

Why does the analysis population matter?

General explanation: an analysis population defines which participants contribute to a result. Different rules for handling missing assessments, early discontinuation, or events before the first scheduled assessment can affect the denominator and potentially the endpoint estimate. The response-evaluable definition in the registry includes pathways for participants who discontinue treatment or experience progression or death before the first post-baseline assessment. The record does not provide participant-level disposition, reasons for missing assessments, or the final analysis-set size, so the application of these rules cannot be checked from the available entries.

The enrollment entry is 18, but enrollment and an endpoint-specific analysis population are not interchangeable concepts. The record does not report a numerical ORR denominator, so an estimate should not be reconstructed by assuming that all listed enrolled participants were analyzed.

What can a single-group design estimate?

General explanation: a single-group study can describe outcomes among participants who received the intervention. A randomized comparator can help estimate how outcomes differ between groups under the trial’s design. This registry record lists no comparator and no random allocation. Thus, even if a response estimate were reported, it would be a description of the study group rather than a randomized estimate of the treatment’s effect relative to another option. Open-label assessment may also be relevant to how investigator-assessed outcomes are interpreted; the registry does not describe a blinded assessment process.

What can be inferred from the analysis entries?

The registry lists 17 outcome measures and zero analysis entries. The outcome descriptions indicate the kinds of measures named in the record, but the absence of analysis entries means numerical estimates and their statistical details are not available in those entries. In particular, the record does not report a hypothesis test, an adjusted analysis, or a statistical plan for the primary endpoint. Those details are not reported in the registry record and should not be inferred from the Phase 2 label or endpoint definition.

General explanation: statistical significance and precision answer different questions. A hypothesis test evaluates compatibility with a specified null model under stated assumptions, while an interval communicates uncertainty around an estimate. Neither alone addresses whether a result is clinically important, whether it is causal, or whether it generalizes beyond the studied group. Since no numerical primary result or test is reported in the registry record, these interpretations cannot be made for this study from the available information.

How should planning calculations be read?

General explanation: sample-size calculations are planning illustrations based on assumptions about an effect, allocation, significance level, and statistical approximation. They are not observations from the trial and do not describe the precision actually achieved. The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of an observed effect. It also states that time-to-event calculations use a total number of events, while other calculations use participants per arm. Those assumptions do not turn this single-group study into a randomized two-arm comparison, and no sample-size illustration should be treated as observed 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("Amivantamab Monotherapy (1050/1400 mg)")
n      <- c(18)
events <- c(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  Amivantamab Monotherapy (1050/1400 mg)  18  0  0.0  0.0  18.5  -0.0  17.6  0.1  17.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary ORR endpoint and secondary measures of response duration, disease control, progression-free survival, overall survival, safety, laboratory and vital-sign abnormalities, and pharmacokinetics. Considering multiple outcomes can raise a multiplicity question: when many statistical comparisons are conducted, the chance of at least one apparently notable finding can increase. General statistical practice may address this through prespecified testing sequences, adjusted significance thresholds, or a clear distinction between confirmatory and exploratory analyses. Which approach, if any, was specified for this study is not reported in the registry record.

The registry record lists zero analysis entries. It does not report a statistical analysis plan, hypothesis tests, multiplicity adjustments, interim analyses, or a sample-size justification. Their absence from the registry record does not establish that they were or were not conducted; those details are not reported in the registry record.

Missing data and analysis populations are also important for the primary endpoint. The registry defines a response-evaluable set using treatment exposure, post-baseline assessment, discontinuation, progression, and death criteria. However, the number in that set, participant disposition, missing-assessment patterns, and the handling of other missing endpoint information are not reported in the registry record. Those details matter because the estimated percentage depends on which participants are included and how outcomes without a complete assessment are classified.

The record also does not report whether the primary endpoint analysis used any adjustment or sensitivity analysis. With no numerical ORR, denominator, confidence interval, or participant-level accounting, readers cannot evaluate how missing assessments or analytic choices may have affected the estimate.

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: ascites (16.7%), diarrhoea (5.6%), tumour haemorrhage (5.6%).

The registry lists 4 participants with serious adverse events among 18 at risk in the amivantamab monotherapy group. It separately lists 18 participants with other adverse events among 18 at risk, and 5 deaths. These are different registry entries; the record does not define their relationship in enough detail to treat them as mutually exclusive categories or to infer that deaths were caused by treatment.

The serious-event terms listed are ascites at 16.7%, diarrhoea at 5.6%, and tumour haemorrhage at 5.6%. These percentages describe the registry’s reported event terms, not a comparison with another group. The record does not provide event-level details, severity grading for each listed term, timing, duration, or attribution to amivantamab. It also does not explain the circumstances surrounding the deaths.

Safety counts describe events recorded in this study group. In general, an event occurring during a study does not by itself establish that the intervention caused it. The absence of a comparator further limits interpretation of whether observed event frequencies differ from what would occur under another treatment or without the study intervention. The figures should therefore be read as descriptive registry entries, not as estimates of comparative risk.

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

The registry record describes a Phase 2, open-label study of amivantamab monotherapy for previously treated advanced hepatocellular carcinoma. It specifies an investigator-assessed ORR endpoint under RECIST version 1.1, defines the response-evaluable analysis set, and lists a 95% confidence interval and assessment timeframe. These details clarify what the primary endpoint was intended to measure.

The record does not report the numerical ORR, its confidence interval, or the number of participants in the response-evaluable analysis set. As a result, the available information cannot establish the observed response rate or how precisely it was estimated. The endpoint definition is not itself an efficacy result.

The study has no listed comparator and is not randomized. It can therefore describe outcomes recorded among participants in the amivantamab group, but cannot estimate a randomized difference from another treatment. The registry’s open-label design is also relevant when interpreting an investigator-assessed endpoint. The record does not report whether independent review was used.

The safety entries include serious adverse events, other adverse events, deaths, and selected serious-event terms. They are descriptive counts and percentages; the record does not establish causation or explain the deaths. Secondary outcome descriptions likewise identify measures but do not provide numerical results.

These limitations mean the registry entries support a careful account of the study’s design, endpoint definitions, and selected safety observations, but not a conclusion about the magnitude or comparative effect of amivantamab. The study’s termination status is recorded, while the reason for termination is not reported in the registry record. A fuller assessment would require results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an outcome estimate are not the same thing. The registry defines ORR using confirmed investigator-assessed responses under RECIST version 1.1, identifies an assessment timeframe, and specifies a confidence interval. Those details describe the planned meaning of the endpoint. Without the numerical estimate, interval, and analysis-set size, however, readers cannot judge the observed response frequency or its precision.

It also illustrates the interpretive limits of a single-group, open-label design. Outcomes in the amivantamab group can be described, but a comparison with a control group is not available in the registry record. That distinction is central to clinical-trial interpretation: a response observed during treatment is not, by itself, a randomized estimate of what would have happened under another treatment.

The registry also separates endpoint definitions from posted analyses. It lists 17 outcome measures but zero analysis entries. This makes it important to distinguish the outcomes a study planned or described from results actually reported in the registry. The secondary outcomes cover efficacy, safety, and pharmacokinetics, but their numerical findings are not reported in the registry record.

Finally, the safety entries demonstrate why event counts need context. Counts, percentages, attribution, timing, and comparison groups answer different questions. The registry reports selected counts and serious-event terms, but does not report event attribution or details around deaths. Statistical reading therefore depends not only on knowing which outcomes were named, but also on having the analysis, denominator, uncertainty, and design information needed to interpret them.

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 main limitation is that the registry record does not report the numerical primary ORR result or its 95% confidence interval. It also does not report the response-evaluable analysis-set size or the number of participants meeting the response definition. The enrollment entry of 18 cannot be assumed to be the endpoint denominator.

The study is open-label and has no listed comparator or random allocation. Consequently, the registry record does not support a randomized comparison with another intervention. The endpoint is investigator-assessed, and whether independent review was used is not reported in the registry record.

The record lists 17 outcome measures and zero analysis entries. Numerical results for the secondary efficacy, safety, and pharmacokinetic outcomes are not reported in the registry record beyond the selected adverse-event entries. A statistical analysis plan, multiplicity strategy, missing-data handling beyond the response-set definition, interim analyses, and sample-size justification are also not reported in the registry record.

The safety information is limited to reported counts, selected serious-event terms, and deaths. Attribution, timing, duration, event-level detail, and the circumstances surrounding deaths are not reported in the registry record. The study is marked terminated, but the reason for termination is not reported in the registry record. These gaps limit both efficacy interpretation and assessment of the completeness and context of the safety findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma — NCT05653427.
• Registry record last updated 2025-01-13; status last verified 2025-01.
• Results first posted 2024-10-30.
• 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 2, open-label, sequential-model study of amivantamab monotherapy in previously treated advanced hepatocellular carcinoma. Allocation is listed as not applicable, masking as none, and no comparator group is listed. The registry records enrollment of 18, a start date of 2022-12-08, a primary completion date of 2023-10-10, and terminated status.

The primary endpoint was investigator-assessed ORR by RECIST version 1.1, with a specified 95% confidence interval and timeframe from treatment start up to 3.8 months. The numerical ORR and confidence interval are not reported in the registry record. Safety entries include 4 participants with serious adverse events among 18 at risk, 18 with other adverse events among 18 at risk, and 5 deaths. The reason for termination and the numerical results for other listed outcomes are not reported in the registry record.