This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors (NCT05063318), a randomized phase 1 study. The primary outcome is Pharmacokinetic Analysis: Dose-adjusted AUC(0-∞).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05063318 |
| Phase | Phase 1 |
| Condition | Advanced Solid Tumors |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | 2 |
| Lead sponsor | PharmaMar |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced solid tumors. The registry describes this as a phase Ib drug-drug interaction study. The pharmacokinetic analysis used data from patients who were evaluable for pharmacokinetic assessment in Part B.
Intervention
Lurbinectedin co-administered with itraconazole, a strong CYP3A4 inhibitor. The registry identifies the combination as ITZ+LRB. The dose used in combination was 0.8 mg/m² in the sequence descriptions.
Comparator
Lurbinectedin alone, identified as LRB Alone. The sequence descriptions use a lurbinectedin dose of 3.2 mg/m² when administered alone.
Primary question
How does itraconazole co-administration relate to lurbinectedin’s dose-adjusted plasma AUC(0-∞), a measure of drug exposure over time? The registry reports a least-squares geometric mean ratio for the comparison, with a 90% confidence interval.
The crossover design places both treatment conditions within the study, with participants assigned to sequence TR or sequence RT. In sequence TR, combination treatment came before lurbinectedin alone; in sequence RT, lurbinectedin alone came before combination treatment. This makes the comparison relevant to a pharmacokinetic interaction question: whether exposure differs between the two treatment conditions under the study’s dosing and assessment schedule.
The registry record does not describe this as a comparison of clinical benefit. It reports pharmacokinetic outcomes, including the primary dose-adjusted AUC(0-∞) measure and secondary measures such as dose-normalized AUC(0-t), dose-normalized Cmax, half-life, clearance, and volume of distribution. The primary question is therefore about drug exposure, not whether treatment changes tumor outcomes or symptoms.
3. Trial Design
This was an open-label, multicenter, randomized, crossover phase Ib study of lurbinectedin with and without itraconazole in patients with advanced solid tumors. The registry lists an enrollment of 14 and describes the study as completed. The recorded start date is 2020-10-07, and the primary completion date is 2022-04-21. Masking is listed as none.
The two randomized sequences differed in the order of the treatment conditions. Sequence TR began with itraconazole plus lurbinectedin 0.8 mg/m² in Cycle 1, followed by lurbinectedin alone at 3.2 mg/m² in Cycle 2. An optional Cycle 3 of lurbinectedin alone at 3.2 mg/m² is also listed. Sequence RT began with lurbinectedin alone at 3.2 mg/m² in Cycle 1, followed by itraconazole plus lurbinectedin 0.8 mg/m² in Cycle 2; it also lists an optional Cycle 3 of lurbinectedin alone at 3.2 mg/m². Each cycle is described as 21 days.
The registry notes that the dose of lurbinectedin given with itraconazole for the initial three patients in Part A was 0.8 mg/m². It also says Part A was meant to ensure the adequacy of the lurbinectedin dose. The pharmacokinetic analysis used data from PK-evaluable patients in Part B, and the same study population was used for the statistical evaluation of the drug-drug interaction.
A crossover structure can support comparison of treatment conditions within a study, while randomizing the order can help address systematic sequence effects. Those are general design considerations, not additional claims about the implementation or analysis of this trial. The registry does not report details such as the sequence-generation method, any washout interval, or the exact terms included in the analysis model. The study is open-label, so treatment assignment was not masked.
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
| Stage | Part A - S1 (TR) | Part B - S1 (TR) | Part B - S2 (RT) |
|---|---|---|---|
| STARTED | 3 | 5 | 6 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 5 | 6 |
Reasons for not completing this period:
| Reason | Part A - S1 (TR) | Part B - S1 (TR) | Part B - S2 (RT) |
|---|---|---|---|
| Progressive disease | 2 | 0 | 3 |
| Compassionate use | 1 | 3 | 3 |
| Adverse Event | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic analysis included data from only PK - evaluable patients from study Part B and the same study population was used to perform the statistical analysis in evaluating the ITZ - lurbinectedin drug-drug interaction. Part A was meant to ensure the adequacy of the dose of lurbinectedin (0.8 mg/m²) when given in combination with itraconazole, and patients (n=3) were not randomized for treatment sequence, so they were not included in the main analysis, as pre-specified in protocol.
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.
| Characteristic | Unit | Part A - S1 (TR) | Part B - S1 (TR) | Part B - S2 (RT) | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 5 | 6 | 14 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 3 | 4 | 8 |
| Age, Categorical: >=65 years | Participants | 2 | 2 | 2 | 6 |
| Age, Continuous | years | 69 (49 to 72) | 64 (56 to 70) | 62 (56 to 72) | 63 (49 to 72) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 4 | 9 |
| Sex: Female, Male: Male | Participants | 0 | 3 | 2 | 5 |
| Race/Ethnicity, Customized: White | Participants | 3 | 5 | 6 | 14 |
| Region of Enrollment: Spain | participants | 3 | 5 | 6 | 14 |
| ECOG PS: 0 | Participants | 1 | 4 | 5 | 10 |
| ECOG PS: 1 | Participants | 2 | 1 | 1 | 4 |
| Weight | kg | 58.9 (49.9 to 73.9) | 66.6 (50.0 to 102.9) | 69.5 (62.8 to 90.5) | 67.5 (49.9 to 102.9) |
| Height | cm | 165 (159 to 171) | 163 (152 to 172) | 166.5 (153 to 182) | 165 (152 to 182) |
| Stage at diagnosis: Early | Participants | 1 | 1 | 2 | 4 |
| Stage at diagnosis: Locally advanced | Participants | 0 | 1 | 2 | 3 |
| Stage at diagnosis: Metastatic | Participants | 2 | 3 | 2 | 7 |
| Primary tumor: Ovarian carcinoma | Participants | 1 | 0 | 3 | 4 |
| Primary tumor: Lung | Participants | 0 | 1 | 2 | 3 |
| Primary tumor: Endometrial carcinoma | Participants | 0 | 2 | 0 | 2 |
| Primary tumor: Colon adenocarcinoma | Participants | 0 | 1 | 0 | 1 |
| Primary tumor: Epidermoid carcinoma | Participants | 0 | 1 | 0 | 1 |
| Primary tumor: Leiomyosarcoma | Participants | 0 | 0 | 1 | 1 |
| Primary tumor: Mesothelioma | Participants | 1 | 0 | 0 | 1 |
| Primary tumor: Pancreatobiliary adenocarcinoma | Participants | 1 | 0 | 0 | 1 |
| Number of sites at baseline | sites | 4 (2 to 4) | 3 (2 to 5) | 2 (1 to 5) | 3 (1 to 5) |
| Sites at baseline: 1 | Participants | 0 | 0 | 2 | 2 |
| Sites at baseline: 2 | Participants | 1 | 2 | 2 | 5 |
| Sites at baseline: 3 | Participants | 0 | 1 | 1 | 2 |
| Sites at baseline: >4 | Participants | 2 | 2 | 1 | 5 |
| Time from diagnosis to first infusion | years | 2.6 (1 to 3.4) | 3.4 (2 to 13.8) | 3.5 (2.5 to 6.8) | 3.4 (1 to 13.8) |
| Prior surgery | Participants | 2 | 3 | 4 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetic Analysis: Dose-adjusted AUC(0-∞), measured over Day 1, 2, 3, 5, 8, 11, 15, 22 (Cycle 1,2,3) (each cycle is 21 days).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | μg·h/L/mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is pharmacokinetic: plasma dose-adjusted AUC(0-∞), reported in μg·h/L/mg. AUC is the area under the concentration-time curve. In general, it summarizes drug exposure across the measured period; the 0-∞ form represents an estimate extending from the start of measurement toward an extrapolated end of the concentration profile. Dose adjustment expresses exposure relative to dose, supporting comparison when the doses used in treatment conditions differ.
Pharmacokinetic endpoints are used in drug-interaction studies because a co-administered medicine can alter the concentration profile of another drug. AUC focuses on overall exposure, while Cmax describes peak concentration and measures such as half-life, clearance, and volume of distribution characterize other features of the concentration-time profile. These measures answer related but distinct questions.
The registry lists sampling on Day 1, 2, 3, 5, 8, 11, 15, and 22 across Cycle 1, Cycle 2, and Cycle 3, with each cycle described as 21 days. The primary endpoint description identifies dose-adjusted plasma AUC(0-∞) as the parameter of interest for statistical analysis. The record does not report further detail about how the extrapolated part of AUC was estimated or how values below assay limits were handled.
This endpoint measures drug exposure, not tumor response, survival, or quality of life. A difference in the pharmacokinetic measure is evidence about exposure under the tested conditions; by itself it does not establish a clinical benefit or harm.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports dose-adjusted AUC(0-∞) geometric means of 288.6 for ITZ+LRB and 105.8 for LRB Alone. The reported least-squares geometric mean ratio is 272.73, with a 90% confidence interval from 213.22 to 348.86. The interval lies on the higher side of the no-change reference for a ratio. In the terms of this pharmacokinetic endpoint, the posted analysis therefore indicates higher dose-adjusted exposure during co-administration than during lurbinectedin-alone treatment.
The confidence interval conveys uncertainty around the estimated ratio. In general, a confidence interval gives a range of values compatible with the data and the method’s assumptions at its stated confidence level. Here, the 90% interval extends from 213.22 to 348.86. It is not a range containing most individual participants’ values, nor does it describe the spread of every measurement. The geometric coefficients of variation reported for the treatment groups, 73.9 for ITZ+LRB and 77.37 for LRB Alone, describe variability on the geometric scale; they are separate from the confidence interval for the ratio.
The registry reports eight observations for each treatment condition in the primary outcome record. The pharmacokinetic analysis population is described as PK-evaluable patients from Part B. Since the design is crossover, these arm-level records should not be read as proof that the treatment conditions involved different sets of people. The registry does not give a participant-level accounting of evaluability or explain any differences between the enrollment figure and the endpoint records.
No p-value is reported for the primary comparison. The ratio and confidence interval give an estimate and an uncertainty range, but the registry record does not provide a test statistic or a p-value to accompany them. Nor does the record state a clinical threshold for what size of exposure difference would be important. The result should therefore be read as a pharmacokinetic estimate under the trial conditions, rather than as a judgment about clinical importance.
The listed secondary outcomes include dose-normalized AUC(0-t), dose-normalized Cmax, T1/2, total body clearance, and volume of distribution. Their presence indicates that the study assessed multiple aspects of pharmacokinetics. The record does not report enough detail to determine whether the secondary outcomes support the same pattern as the primary outcome, and values missing or not estimable for a two-arm comparison are noted for other outcome material. No clinical efficacy outcome is described in the posted primary result.
These findings apply to the study’s advanced-solid-tumor population, dosing sequences, and pharmacokinetic analysis population. They should not be generalized automatically to other populations, doses, or treatment settings. The registry does not report a detailed account of the analysis assumptions, possible period effects, or the handling of all missing pharmacokinetic observations.
9. Statistical Methods Explained
The reported primary comparison uses an ANOVA and presents its result as a least-squares geometric mean ratio. ANOVA is a general method for comparing group means while accounting for terms specified in a model. In a crossover study, model specification can matter because observations may reflect treatment, sequence, period, or participant-level features. The registry names ANOVA but does not report the model terms, coding, or diagnostics, so those details cannot be assessed from the record.
What does a geometric mean ratio describe?
A geometric mean is useful for measurements that are positive and may vary multiplicatively rather than additively. A ratio compares the geometric mean under one condition with the geometric mean under another. The registry’s reported ratio is 272.73 for ITZ+LRB relative to LRB Alone, with a 90% confidence interval of 213.22 to 348.86. Since the interval remains above the no-change reference, the estimate points toward higher dose-adjusted exposure with co-administration. This is a comparison of group-level exposure summaries, not a description of every participant’s response.
Least-squares means are model-based estimates: they reflect the fitted analysis rather than necessarily being the raw arithmetic summaries. The record does not state which covariates or design terms were included, so the exact adjustments behind the reported ratio are not reported in the registry record. The reported treatment-group geometric means are 288.6 and 105.8, with geometric coefficients of variation of 73.9 and 77.37, respectively. These summaries provide context but do not replace the model-based ratio.
How should the confidence interval be read?
A confidence interval expresses uncertainty in an estimate under the method’s assumptions. It is not an individual-level range and does not guarantee that the true effect lies within the interval. A wider interval indicates less precision than a narrower interval on the same scale. For this result, the confidence level is 90%, and the reported limits are 213.22 and 348.86. The registry gives no p-value for this analysis, and a p-value should not be inferred from the interval or reconstructed from rounded values.
The ratio scale has a no-change reference, and the reported interval is entirely on one side of it. This supports describing the estimated comparison as directionally distinct from no change under the reported analysis. It does not establish the size of a clinically meaningful effect, because the registry does not specify such a threshold. Statistical uncertainty and clinical relevance are separate questions.
Why does the crossover design matter?
In general, a crossover design lets each participant receive more than one treatment condition, so comparisons can account for stable participant characteristics. Randomizing treatment order can reduce systematic differences in which condition comes first. However, period effects, sequence effects, and carryover can influence interpretation. The registry lists sequences TR and RT, but it does not report how these potential effects were handled in the ANOVA or whether a washout interval was used. This prevents a detailed independent assessment of the design-specific modeling.
The endpoint schedule lists assessments on Day 1, 2, 3, 5, 8, 11, 15, and 22 across cycles. Dense concentration-time sampling can inform estimates of exposure and other pharmacokinetic features. The record does not describe assay procedures, the calculation method for AUC(0-∞), or the assumptions used to extrapolate the concentration profile. Those omissions limit assessment of measurement and estimation choices.
What do planning calculations mean?
Any sample-size planning illustration based on an observed effect is not the trial’s observed power. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Such calculations describe hypothetical planning scenarios under those assumptions. They are not evidence that the study had a particular probability of detecting an effect, and they do not substitute for the actual analysis or the trial’s design rationale. The trial’s own sample-size justification is not reported in the registry record.
The summary statistics and interval are already rounded in the registry. A recalculation from rounded summaries can differ from a sponsor analysis because of rounding or because the sponsor used participant-level data and model details not available in summary results. No discrepancy is flagged for this comparison, but the registry record does not provide the full analysis dataset or enough model detail to reproduce the sponsor’s result independently.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANOVA | Least-squares geometric mean ratio 272.73 | 213.22 to 348.86 | not reported |
The registry reports the sponsor’s primary analysis as an ANOVA-based least-squares geometric mean ratio of 272.73 for ITZ+LRB relative to LRB Alone. Its 90% confidence interval is 213.22 to 348.86. The comparison is reported without a p-value. The group geometric means are 288.6 for ITZ+LRB and 105.8 for LRB Alone.
A simple unadjusted recalculation from posted summary statistics, when available, is not equivalent to the sponsor’s model-based analysis. The sponsor’s analysis uses an ANOVA and reports a least-squares ratio, whereas a recalculation from summary values cannot reproduce participant-level modeling or any adjustments not described in the record. The registry does not flag a discrepancy between the posted result and the recalculation.
The sponsor analysis should therefore be treated as the primary reported analysis. The record does not provide the underlying participant-level data, full model specification, or enough information to independently recreate the least-squares estimate. This does not change the meaning of the reported result: it is an estimate of relative dose-adjusted exposure under the study conditions, with uncertainty expressed by the stated interval.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary pharmacokinetic outcome, dose-adjusted AUC(0-∞), and five secondary pharmacokinetic outcomes: dose-normalized AUC(0-t), dose-normalized Cmax, T1/2, total body clearance, and volume of distribution. Assessing several outcomes raises a general multiplicity consideration: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. Whether and how to address that issue depends on the prespecified analysis plan.
The registry record does not report a multiplicity-adjustment procedure, a hierarchy for interpreting secondary outcomes, or a broader statistical analysis plan. It also does not report p-values for the primary comparison. The available primary estimate and confidence interval can be described as posted, but the record does not support reconstructing the family of tests or determining how confirmatory the secondary analyses were intended to be.
The pharmacokinetic analysis is described as including only PK-evaluable patients from Part B, with the same study population used for the statistical evaluation of the itraconazole-lurbinectedin interaction. The registry does not report a detailed definition of PK-evaluable, a participant flow by sequence, or reasons for exclusion from that analysis. It also does not explain how missing samples or incomplete concentration profiles were handled.
The registry indicates that values are missing or not estimable for a two-arm comparison for other outcome material, but does not identify in that note which particular measures are affected. The record lists five secondary outcomes, yet the available information does not allow a complete assessment of their estimates or missingness. Missingness can matter if the availability of measurements is related to treatment, exposure, or participant characteristics; whether that occurred in this study is not reported in the registry record.
The crossover structure also makes the analysis population and period-specific availability important. The record provides treatment-condition counts for the primary endpoint but does not give a full account of paired observations or incomplete treatment sequences. The extent to which missing data could alter the comparison therefore cannot be evaluated from the registry information.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| ITZ+LRB Cycle | 4 | 13 | 30.8% |
| LRB Alone Cycle | 5 | 14 | 35.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ITZ+LRB Cycle | 1 of 13 |
| LRB Alone Cycle | 1 of 14 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ITZ+LRB Cycle | 12 of 13 |
| LRB Alone Cycle | 13 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | ITZ+LRB Cycle | LRB Alone Cycle |
|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 1 of 13 | 1 of 14 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 1 of 14 |
| Small intestinal obstruction | Gastrointestinal disorders | 1 of 13 | 1 of 14 |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | 1 of 13 | 1 of 14 |
| Intestinal obstruction | Gastrointestinal disorders | 1 of 13 | 1 of 14 |
| Deep vein thrombosis | Vascular disorders | 0 of 13 | 1 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ITZ+LRB Cycle | LRB Alone Cycle |
|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 7 of 13 | 7 of 14 |
| Nausea | Gastrointestinal disorders | 5 of 13 | 5 of 14 |
| Vomiting | Gastrointestinal disorders | 4 of 13 | 4 of 14 |
| Fatigue | General disorders | 4 of 13 | 4 of 14 |
| Constipation | Gastrointestinal disorders | 1 of 13 | 1 of 14 |
| Bone pain | Musculoskeletal and connective tissue disorders | 1 of 13 | 1 of 14 |
| Dysgeusia | Nervous system disorders | 1 of 13 | 1 of 14 |
| Syncope | Nervous system disorders | 1 of 13 | 1 of 14 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 1 of 14 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 1 of 14 |
Serious events with the highest arm-level rate: alanine aminotransferase increased (7.7%), pleural effusion (7.7%), small intestinal obstruction (7.7%), rhabdomyolysis (7.7%), intestinal obstruction (7.7%).
The registry reports serious adverse events by treatment cycle. For the ITZ+LRB Cycle, 13 were at risk and 4 were affected; for the LRB Alone Cycle, 14 were at risk and 5 were affected. Deaths are listed as 1 in each cycle group. These are descriptive counts, not an adjusted comparison of safety between treatment conditions.
The registry also lists serious adverse event terms with percentages: Alanine aminotransferase increased, Pleural effusion, Small intestinal obstruction, Rhabdomyolysis, and Intestinal obstruction are each listed as 7.7%; Deep vein thrombosis is listed as 7.1%. These entries describe events recorded in the registry and should not be interpreted as evidence that the treatment condition caused them. The record does not provide enough detail to assess timing, attribution, severity beyond the serious-event classification, or participant-level overlap among events.
Because the study uses a crossover design, cycle-group counts do not necessarily represent separate groups of participants. The numbers at risk differ between the listed cycle groups, and the registry does not explain the reasons for that difference. Counts across periods are not directly comparable without accounting for exposure time, sequence, and the study’s safety-analysis methods. The registry record does not report a detailed statistical comparison of adverse events.
13. What the Result Does, and Does Not, Mean
The main statistical result is a reported least-squares geometric mean ratio of 272.73 for dose-adjusted AUC(0-∞) during itraconazole plus lurbinectedin compared with lurbinectedin alone. The 90% confidence interval, 213.22 to 348.86, lies entirely on the higher side of the no-change reference. The result therefore describes higher estimated dose-adjusted plasma exposure during co-administration under the conditions tested.
This is a pharmacokinetic finding. It does not establish whether any change in exposure leads to a change in tumor response, survival, symptoms, or quality of life. The registry does not report those as the primary question, and no clinical outcome conclusion should be inferred from AUC alone. The record also does not state a threshold for a clinically important exposure difference.
The estimate applies to the study’s treatment conditions and PK-evaluable Part B population. It should not automatically be extended to different doses, patient populations, or clinical settings. The registry describes a small phase Ib study with open-label treatment and a crossover structure; the full analysis model and handling of potential period or carryover effects are not reported.
The confidence interval communicates uncertainty in the ratio estimate but does not indicate the range of individual participant outcomes. The geometric coefficients of variation show that variability was also reported for each treatment condition. A group-level estimate can coexist with meaningful variation among participants, and the registry record does not provide individual-level distributions for further assessment.
There is no reported p-value for the primary analysis, and the registry does not describe multiplicity procedures for the secondary outcomes. These omissions limit broader claims about formal statistical testing. The strongest supported reading is narrow: the sponsor’s posted analysis estimates a difference in dose-adjusted lurbinectedin exposure between the two treatment conditions, with the reported interval indicating uncertainty around that estimate. It does not by itself establish a clinical effect or a general rule for treatment.
14. Why This Trial Matters Statistically
This study illustrates how a clinical trial can address a drug-interaction question through pharmacokinetic endpoints rather than patient-centered efficacy outcomes. AUC(0-∞) summarizes exposure across a concentration-time profile, while accompanying measures such as Cmax, half-life, clearance, and volume of distribution describe other features. Considering these measures helps distinguish an overall exposure comparison from a complete account of a medicine’s pharmacology.
The randomized crossover design is also statistically instructive. In general, having treatment conditions occur in different orders can support within-study comparisons, while also making sequence, period, and carryover considerations relevant. The registry identifies the two sequences but does not report enough analysis detail to assess how these design features entered the model. That distinction between a design’s potential advantages and the documentation of its actual analysis is important when interpreting registry results.
The reported geometric mean ratio and confidence interval show why effect estimates and uncertainty should be read together. The ratio gives the direction and scale of the reported exposure comparison; the interval conveys precision under the analysis method. Neither alone answers whether the difference is clinically important. That question requires context and thresholds not reported in the registry.
The record also highlights how analysis populations and missing measurements matter in pharmacokinetic studies. The primary analysis used PK-evaluable patients from Part B, but the criteria and participant-level accounting are not described. Without that information, readers cannot fully assess how evaluability and incomplete profiles might affect the estimate.
Finally, safety counts in a crossover study need contextual interpretation. Period-specific counts and at-risk figures are descriptive, and they do not by themselves provide a causal or adjusted comparison. The study therefore offers a focused example of the need to separate pharmacokinetic evidence, safety description, and clinical benefit claims.
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’s summary leaves important details of the statistical analysis unspecified. It identifies ANOVA and a least-squares geometric mean ratio, but does not describe model terms, transformations, diagnostics, or handling of sequence and period effects. It also does not report whether carryover was assessed or whether a washout interval was used. These omissions limit independent evaluation of the crossover analysis.
The pharmacokinetic analysis population is restricted to PK-evaluable patients from Part B, but the record does not define evaluability or provide a detailed flow by sequence and treatment period. The endpoint record lists eight observations for each condition, while overall enrollment is 14; the registry does not explain the relationship between these counts. The paired-observation structure and handling of incomplete profiles are not reported.
Details of pharmacokinetic measurement and calculation are also absent. The record does not describe the assay, the handling of concentrations below quantification limits, or the method and assumptions used to estimate AUC(0-∞). Those choices can affect exposure estimates, particularly the extrapolated part of the profile.
The posted primary result includes a confidence interval but no p-value. The record does not state a clinical threshold for an important exposure difference or describe a multiplicity strategy for the listed secondary outcomes. Some outcome material is noted as missing or not estimable for a two-arm comparison, without specifying which measures. Consequently, the secondary evidence cannot be fully assessed from the registry record.
Finally, this is an open-label phase Ib study in patients with advanced solid tumors, and its primary outcome is pharmacokinetic rather than clinical efficacy. The safety counts are descriptive and do not provide an adjusted causal comparison. These limitations restrict what can be concluded beyond the posted exposure estimate and its stated uncertainty.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Clinical Trial of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors — NCT05063318.
- Registry record last updated 2025-09-02; status last verified 2025-08.
- Results first posted 2025-09-02.
- 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.
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19. Record Summary
The registry record describes a completed, open-label, randomized crossover phase Ib study of lurbinectedin with and without itraconazole in patients with advanced solid tumors. Enrollment is listed as 14. The study started on 2020-10-07, with primary completion on 2022-04-21, and PharmaMar is listed as sponsor.
The primary endpoint is dose-adjusted plasma AUC(0-∞). The reported least-squares geometric mean ratio for ITZ+LRB versus LRB Alone is 272.73, with a 90% confidence interval of 213.22 to 348.86. The pharmacokinetic analysis used PK-evaluable patients from Part B. Secondary outcomes include additional exposure and disposition measures, but the registry record does not provide a complete account of their results or missingness.
The result supports a focused interpretation about estimated drug exposure under the tested conditions. It does not establish clinical benefit, and the registry does not report enough statistical detail to independently reproduce the sponsor’s model or evaluate every analysis assumption.