Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors (NCT02454972), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

The study was described as a multicenter, open-label, exploratory phase II clinical trial assessing lurbinectedin in previously treated patients with advanced solid tumors. Its clinical question is therefore about the frequency of confirmed tumor responses in the study population, rather than a difference between randomized treatments. With no comparator arm, the trial cannot directly estimate a treatment contrast against another therapy or against a control condition.

The response definition uses tumor measurements: complete response requires disappearance of all target lesions, while partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions compared with baseline. The registry also defines progressive disease and stable disease, but these categories do not count as confirmed responses for the primary outcome. The outcome timeframe extends from treatment start to progression, a subsequent therapy, or the end of follow-up, until Cycle 6, with each cycle lasting 21 days.

The central interpretive issue is that the registry record supplies the endpoint definition and its confidence-interval type, but not the primary result. The response percentage, its precision, and the number of patients included in that analysis are not reported in the registry record.

3. Trial Design

This is a completed, multicenter, open-label phase II trial of lurbinectedin (PM01183) in previously treated patients with advanced solid tumors. The registry describes its purpose as exploratory and its design as a single-group study. It lists allocation as not applicable and masking as none. Enrollment is recorded as 345, but that is not necessarily the size of the primary-outcome analysis population: the registry identifies that population as treated patients with disease measurement, and its size is not reported in the registry record.

The intervention is lurbinectedin, described in the arm information as 4 mg vials of powder for concentrate for solution for infusion. No concurrent control arm is listed. Consequently, the study is not a randomized treatment comparison, and its design does not support a direct estimate of how outcomes differ between lurbinectedin and another assigned treatment. Any comparison with external experience would require information and assumptions not reported in the registry record.

The primary outcome is overall response rate, defined as the percentage of patients with a confirmed complete or partial response according to RECIST v.1.1. Its timeframe runs from treatment start to progression, the start of subsequent therapy, or the end of follow-up, until Cycle 6; a cycle is described as 21 days. The registry also lists secondary outcomes including duration of response, clinical benefit, disease control rate, progression-free survival, progression-free survival at 4 and 6 months, overall survival, and overall survival at 6 months. Although the record lists 11 outcome measures, it gives no corresponding analyses.

The recorded study start date is 2015-08-25, primary completion date is 2020-09-18, and status is completed. The registry record does not report a detailed statistical analysis plan, a rationale for the enrollment target, interim analyses, or outcome-specific analysis populations beyond the primary endpoint population description. Those omissions limit assessment of how the study planned to handle uncertainty, multiplicity, and incomplete observations.

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.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treated patients and with disease measurement

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: Treated patients only

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR), measured over From the start of treatment to the date of progression or the start of a subsequent therapy or end of patient's follow-up, until Cycle 6 (21-day cycle).

Overall response rate is the percentage of patients with a confirmed complete response or partial response. In this trial, the response categories follow RECIST v.1.1 criteria. A complete response means disappearance of all target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions compared with baseline. Progressive disease and stable disease are separately defined in the registry, and neither is counted as a response for this endpoint.

Response rate is used in clinical trials as a concise measure of the proportion of assessed patients meeting a prespecified tumor-response definition. It turns individual response classifications into a proportion, while the confidence interval describes uncertainty around that proportion. The interval matters because a percentage alone does not show how precisely the underlying response frequency has been estimated. These are general statistical interpretations, not additional findings from this trial.

The registry specifies a 95% confidence interval and identifies the population as treated patients with disease measurement. It states that the timeframe begins at treatment start and continues to progression, subsequent therapy, or the end of follow-up, until Cycle 6, with a 21-day cycle. The endpoint is therefore tied to both a defined response standard and a specified observation period.

The registry record does not report the observed response percentage, the interval limits, or the number of patients contributing to the endpoint. Thus, the endpoint's definition can be described, but its trial result and precision cannot be evaluated from the registry record. The enrollment count does not replace the missing endpoint-specific denominator.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Overall response rate is a binary-outcome summary: each patient in the endpoint population is classified according to whether a confirmed complete or partial response occurred. The group result is expressed as a percentage. This is a general explanation of the statistical form of the endpoint; the registry record does not report the actual percentage or the number of patients analyzed.

What does a confidence interval add?

A confidence interval expresses uncertainty in an estimate. For a response percentage, it indicates the range of values that are reasonably compatible with the observed data under the method used to construct the interval. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. It is not a guarantee that the true value lies within a particular interval, nor does it describe variation in outcomes for an individual patient. These are general statistical interpretations.

The registry specifies a 95% confidence interval for the primary outcome but does not report its limits or the method used to calculate it. Without the estimate, interval, and endpoint denominator, the precision of the response rate cannot be evaluated. The enrollment count alone cannot supply these missing elements because not every enrolled participant necessarily belongs to the defined treated-and-measured population.

Why does the analysis population matter?

The primary outcome population is described as treated patients with disease measurement. This identifies a broad eligibility condition for the endpoint, but the registry does not state how many patients met it, whether every such patient had an evaluable follow-up assessment, or how missing tumor measurements were handled. The denominator affects a proportion, and decisions about unobserved outcomes can affect its interpretation. These details are not reported in the registry record.

In general, an analysis should state who was included, how response was confirmed, and what happened when assessment data were incomplete or not obtained. The response criteria define what counts as a response, but they do not by themselves describe how ambiguous assessments, early discontinuation, or missing measurements were treated. The registry record does not report these operational or analytical details.

What does a single-group design estimate?

A single-group study estimates outcomes observed among participants receiving the study intervention, subject to the study's population, follow-up, and assessment procedures. It does not create a concurrent randomized control group. Without such a group, an outcome proportion is not a randomized estimate of the difference attributable to treatment. General comparisons to historical outcomes would require a suitable external source and careful assumptions; those are not described in the registry record.

The trial is open-label, with masking recorded as none. In general, masking can reduce the potential for expectations or knowledge of treatment to influence some assessments or decisions. Its relevance depends on the endpoint and safeguards used. The registry record does not describe independent review, assessor procedures, or other safeguards, so their presence or absence cannot be determined from the record.

What can be inferred from the planning illustrations?

The record describes sample-size planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not a description of the actual single-group trial design. The illustrations are not the trial's own design justification, and they should not be interpreted as observed power. No planning illustration results or effect fractions are reported in the registry record.

In general, a sample-size illustration asks how much information a hypothetical study might need to detect a chosen effect under specified assumptions. Such an exercise depends on the effect used, the outcome model, allocation, significance level, and desired power. It does not show that a completed trial had a particular probability of detecting its actual effect. The registry record does not report a study-specific sample-size justification or statistical power calculation.

Why can over-dispersion matter?

For some outcomes, observations vary more than a simple statistical model expects. This is called over-dispersion. If it is ignored, uncertainty estimates can be too optimistic. This general issue may matter for count or rate outcomes, but the primary endpoint is a response percentage, and the registry does not identify a model or report analysis details that would allow assessment of over-dispersion. No conclusion about the analysis method should be inferred.

Finally, the registry lists 11 outcome measures but reports zero analyses. Listing outcomes is not equivalent to posting estimates, confidence intervals, or hypothesis tests. The record does not identify an inferential strategy for the primary or secondary outcomes, nor does it describe whether analyses were adjusted or how multiplicity was addressed. These absences constrain statistical interpretation.

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("Biliary Tract Carcinoma Cohort", "Carcinoma of Unknown Primary Site Cohort", "Endometrial Carcinoma Cohort", "Ewing's Family of Tumors Cohort", "Germ Cell Tumors Cohort", "Head and Neck Carcinoma Cohort")
n      <- c(18, 19, 71, 28, 23, 13)
events <- c(1, 0, 8, 4, 1, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Biliary Tract Carcinoma Cohort  18  1  5.6  0.1  27.3  1.0  25.8  1.3  26.0
ARM  Carcinoma of Unknown Primary Site Cohort  19  0  0.0  0.0  17.6  0.0  16.8  0.1  16.8
ARM  Endometrial Carcinoma Cohort  71  8  11.3  5.0  21.0  5.8  20.7  5.9  20.7
ARM  Ewing's Family of Tumors Cohort  28  4  14.3  4.0  32.7  5.7  31.5  5.8  31.7
ARM  Germ Cell Tumors Cohort  23  1  4.3  0.1  21.9  0.8  21.0  1.0  21.1
ARM  Head and Neck Carcinoma Cohort  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including overall response rate and several secondary measures of response, disease control, progression, and survival. It reports no analyses. The record therefore does not provide estimates or tests for the primary and secondary outcomes, and it does not describe an analysis hierarchy or a plan for interpreting multiple outcomes.

Multiplicity arises when several outcomes or statistical tests are considered. In general, testing many hypotheses can increase the chance of at least one apparently notable result arising by chance. Statistical plans may address this through prespecified ordering, adjusted significance thresholds, or other approaches. The registry record does not report whether any such approach was planned or used. The outcome list alone does not establish that all listed measures were formally tested.

The record identifies the primary endpoint population as treated patients with disease measurement, but gives no count for that group. It also does not report how missing tumor measurements, incomplete follow-up, or other unavailable outcome data were handled. In general, missing data can affect both the denominator and the estimated proportion, depending on why data are missing and how the analysis treats them. The registry does not provide enough information to assess these issues for this trial.

The statistical analysis plan, interim analyses, and sample-size justification are not reported in the registry record. The planning illustrations described in the record use hypothetical assumptions and are not the trial's own design plan. Consequently, the available registry information does not establish how the study handled multiplicity, missingness, or analysis-population decisions.

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: febrile neutropenia (6.0%), neutropenia (4.5%), general physical health deterioration (4.5%), thrombocytopenia (3.6%), abdominal pain (3.3%).

The registry lists one lurbinectedin safety group. It records 335 participants at risk for serious adverse events and 136 affected. For other adverse events, it lists 335 at risk and 330 affected. Deaths are listed as 261. These are posted safety counts; they should be read separately from the primary response endpoint and should not be treated as evidence that the intervention caused an event or death.

The serious-event terms with the largest listed percentages are febrile neutropenia at 6.0%, neutropenia at 4.5%, general physical health deterioration at 4.5%, thrombocytopenia at 3.6%, abdominal pain at 3.3%, and anaemia at 3.0%. The registry reports these values as percentages, but does not provide further event-level detail in the record.

Adverse-event categories can have different definitions and reporting conventions. In general, a participant may experience more than one event, so event counts or percentages should not be summed to infer the number of affected participants. The registry record does not state whether the listed serious-event terms overlap, how long each participant was followed for safety, or whether deaths were considered treatment-related. These figures alone do not establish causation or comparative risk, particularly because the study has no control group.

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

The registry record describes a completed phase II, open-label, single-group study of lurbinectedin in previously treated patients with advanced solid tumors. Its primary endpoint is a confirmed response percentage, defined using RECIST v.1.1 and assessed over the stated treatment and follow-up period. This provides a clear description of what the primary outcome was intended to measure.

However, the primary result itself is not reported in the registry record. The observed overall response rate, its 95% confidence interval, and the size of the primary-outcome analysis population are absent. It is therefore not possible to describe the trial's response frequency or how precisely it was estimated from this record. The enrollment count is not a substitute for the missing endpoint-specific result or denominator.

The single-group design also means that the record does not establish a randomized comparison with another treatment or a control condition. In general, outcomes observed in one group can be described, but differences from outcomes in other settings may reflect differences in participants, assessment, follow-up, or other factors. No direct comparative treatment effect can be estimated from the design described in the registry.

The record lists selected safety counts and serious adverse-event percentages. These provide descriptive information as posted, but do not by themselves establish that treatment caused the events or deaths. A comparator and additional context would be needed for a comparative safety interpretation. The registry record does not report attribution details for the deaths.

The appropriate reading is therefore bounded: the record defines the question and reports some design and safety information, but does not report the primary efficacy estimate or analyses of the listed secondary outcomes. It neither supports a quantitative conclusion about response nor supplies evidence for a treatment comparison. Missing outcome results should not be interpreted as either favorable or unfavorable findings.

14. Why This Trial Matters Statistically

This trial is statistically notable as an example of why endpoint definitions, analysis populations, and reported results must be considered separately. The registry defines overall response rate in terms of confirmed complete or partial response and specifies a 95% confidence interval. Yet it does not report the response estimate, interval limits, or analysis denominator. A well-defined endpoint is necessary for interpretation, but definition alone does not reveal what the study observed.

The study's single-group structure is also central. Its design addresses the frequency of response among treated participants, rather than a randomized difference between treatment assignments. This distinction matters because descriptive outcomes and comparative effects answer different questions. A response percentage from a single group, if reported, would still need to be interpreted in light of the population and outcome assessment process.

The record further illustrates the difference between enrollment and endpoint analysis. Enrollment is listed as 345, but the primary population is defined as treated patients with disease measurement, and its size is not reported in the registry record. The endpoint-specific denominator is important for understanding a proportion and its precision; it cannot be safely replaced with the overall enrollment figure.

Finally, the registry lists a range of secondary outcomes but reports no analyses. Outcomes registered in advance can clarify what investigators intended to assess, but they do not substitute for estimates, uncertainty intervals, or analysis methods. The statistical record is therefore informative about trial structure and planned measurement, while remaining insufficient for evaluating the primary result or drawing comparative conclusions.

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.

Several trial-specific limitations of interpretation follow directly from the registry record. The primary endpoint is defined, but its observed response percentage, 95% confidence interval, and analysis denominator are not reported in the registry record. Without these, the central efficacy outcome cannot be quantified or assessed for precision.

The study is single-group, with allocation listed as not applicable and masking as none. There is no randomized comparator in the record. This precludes a direct randomized estimate of a difference between lurbinectedin and another treatment. The open-label design is documented, but the registry record does not describe response-review procedures or whether independent assessment was used.

The registered enrollment is 345, while the outcome population is described as treated patients with disease measurement. The count in that population and the handling of patients without measurable follow-up are not reported in the registry record. The record also does not report how missing data or incomplete assessments were handled.

Although 11 outcome measures are listed, no analyses are reported. The registry does not describe an analysis hierarchy, multiplicity handling, interim analyses, or a detailed statistical analysis plan. It also does not report a study-specific sample-size justification. The planning illustrations described in the record are not the trial's own design rationale and should not be interpreted as observed power.

Safety interpretation is limited as well. Counts and selected serious-event percentages are posted, but event overlap, follow-up duration, and attribution of deaths are not reported in the registry record. The lack of a control group also limits comparative safety interpretation. These limitations do not imply a particular direction of effect; they identify what cannot be established from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors — NCT02454972.
• Registry record last updated 2023-03-02; status last verified 2023-02.
• Results first posted 2021-11-22.
• 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 NCT02454972, a completed, multicenter, open-label, exploratory phase II single-group trial of lurbinectedin (PM01183) in previously treated patients with advanced solid tumors. Enrollment is listed as 345. The recorded start date is 2015-08-25 and the primary completion date is 2020-09-18.

The primary outcome is overall response rate, defined as the percentage of treated patients with disease measurement who had a confirmed complete or partial response according to RECIST v.1.1. The registry specifies a 95% confidence interval and an assessment period extending until Cycle 6, with 21-day cycles. The observed response result, confidence limits, and endpoint analysis population size are not reported in the registry record.

The record lists secondary response, progression, and survival outcomes, but reports no analyses. It also includes descriptive safety counts and selected serious adverse-event percentages. The single-group design does not provide a randomized comparator, and the registry record does not report a detailed statistical analysis plan, missing-data approach, or study-specific sample-size justification.