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 Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma (NCT03436732), a non-randomized phase 1 study. The primary outcome is Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03436732 |
| Phase | Phase 1 |
| Condition | Mesothelioma |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes adults ages 18 and older with pleural or peritoneal mesothelioma that had not responded to prior platinum-based therapy. The listed condition is mesothelioma. The study enrolled 5 participants. Further details about the characteristics of those participants are not reported in the registry record.
Intervention
Participants received LMB-100 in combination with SEL-110. The study included dose escalation and dose expansion: the first arm used escalating doses, and the second used the recommended phase 2 dose. The registry summary describes treatment in 21-day cycles for up to 4 cycles.
Comparator
There was no randomized control group. The registry describes two dose groups receiving the combination, at 140 mcg/kg and 100 mcg/kg. These sequential dose groups are not a like-for-like control comparison, so differences between them cannot be interpreted as if participants had been randomly assigned to otherwise comparable groups.
Primary question
The primary endpoint asks how many participants had grade 3 or higher adverse events related to study drug at the listed dose levels, assessed at Day 85. The registry also lists response, detectable LMB-100 after Cycle 4, and serious and non-serious adverse events as secondary outcomes. The primary endpoint result by dose and grade is not reported in the registry record.
3. Trial Design
This was a Phase I, non-randomized, unmasked, sequential study sponsored by the National Cancer Institute. The registry lists an enrollment of 5 and a status of terminated. The recorded start date is 2018-02-28, and the primary completion date is 2019-04-30. The reason for termination is not reported in the registry record.
The study evaluated LMB-100 with SEL-110 in people with malignant pleural or peritoneal mesothelioma. The registry describes one dose-escalation arm, in which participants received the combination at escalating doses, and one dose-expansion arm, in which participants received the combination at the recommended phase 2 dose. The posted arm descriptions identify 140 mcg/kg and 100 mcg/kg dose levels in the primary endpoint title and safety summary. Allocation was not randomized; the registry labels the model sequential. No masking was used.
The brief summary describes screening with medical history, physical examination, blood and urine tests, tumor tissue review, imaging, and heart-function tests. Treatment was planned in 21-day cycles for up to 4 cycles. LMB-100 was administered intravenously on day 1, day 3, and day 5 of each cycle; SEL-110 was administered intravenously on day 1. These are descriptions of the study schedule, not evidence that every participant completed every cycle.
Because the groups were sequential dose groups rather than randomized comparison groups, their outcomes should not be read as a controlled estimate of a dose effect. The total enrollment was 5, and the registry does not report participant flow, group-specific enrollment beyond the safety at-risk counts, or reasons for discontinuation.
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: 1/5 participants enrolled was a screen failure following enrollment.
Overall Study
| Stage | 140 mcg/kg LMB-100 + SEL-110 | 100 mcg/kg LMB-100 + SEL-110 |
|---|---|---|
| STARTED | 4 | 1 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 1 |
Reasons for not completing this period:
| Reason | 140 mcg/kg LMB-100 + SEL-110 | 100 mcg/kg LMB-100 + SEL-110 |
|---|---|---|
| Not treated-enrolled in different study | 1 | 0 |
| Off study after cycle 1 | 1 | 0 |
| Adverse Event | 2 | 0 |
| Death | 0 | 1 |
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 | 140 mcg/kg LMB-100 + SEL-110 | 100 mcg/kg LMB-100 + SEL-110 | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 1 | 5 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 1 | 4 |
| Age, Categorical: >=65 years | Participants | 1 | 0 | 1 |
| Age, Continuous | years | 65.75 (SD 2.278) | 58 (SD 0) | 63 (SD 5.86) |
| Sex: Female, Male: Female | Participants | 2 | 0 | 2 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 | 1 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 4 | 1 | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 4 | 1 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg, measured over Day 85.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with grade 3 or higher adverse events related to study drug at dose levels 140 mcg/kg and 100 mcg/kg, assessed at Day 85. It is a count endpoint: it asks how many participants met the event definition, rather than measuring an average change in a laboratory value or symptom score. The registry says adverse events were assessed using CTCAE v5.0.
The endpoint description characterizes grade 3 events as severe or medically significant, potentially requiring hospitalization or limiting self-care activities; grade 4 events as having life-threatening consequences; and grade 5 as death related to an adverse event. These categories describe severity. The endpoint also specifies that events must be related to study drug, making attribution part of the outcome definition.
In an early-phase study, a safety endpoint is used to describe adverse events observed during exposure and to inform evaluation of the regimen and dose levels. That general purpose does not mean this record establishes a tolerable dose or a safety profile. The registry record does not report the primary endpoint counts by grade and dose, nor does it provide a detailed attribution procedure. The posted adverse-event summary should therefore not be treated as a substitute for the missing primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record supports a descriptive account of adverse events in a very small study, not a reliable comparison between dose levels. The registry lists 5 participants overall. In the safety summary, the 140 mcg/kg group has 4 participants at risk for serious adverse events and 3 in the affected count; the 100 mcg/kg group has 1 participant at risk and 1 in the affected count. The same at-risk and affected counts are listed for other adverse events. These counts are the posted safety figures; they do not by themselves establish that events were caused by treatment.
The deaths column lists 2 for the 140 mcg/kg group and 1 for the 100 mcg/kg group. The registry does not report the causes of these deaths or establish their relationship to study drug in this summary. They should not be interpreted as treatment-related deaths. Likewise, the listed serious-event terms include lung infection and pneumonitis at 100.0%, disease progression at 50.0%, and atrial fibrillation, capillary leak syndrome, and dyspnea at 25.0%. The denominator and calculation basis for these percentages are not reported in the registry record. They are not incidence estimates for a broader patient population.
The primary endpoint specifically concerns grade 3 or higher events related to study drug at Day 85. The group-level safety counts do not supply the missing detail about which events were grade 3 or higher, how many met the study-drug relationship criterion, or how events were distributed across grades. The primary endpoint result is therefore not reported in the registry record. The secondary outcomes include partial or complete response, detectable LMB-100 in blood after Cycle 4, and serious and non-serious adverse events, but their results are not reported in the record.
As general statistical context, small counts are imprecise: each participant represents a substantial part of the observed group, and a count can change materially if one participant’s status differs. The sequential, non-randomized design also leaves dose groups open to differences in timing, participant characteristics, or follow-up. No adjustment for such differences is reported. Thus, the observed counts describe what was recorded in this study; they do not quantify a comparative treatment effect or establish how often the events would occur in a larger population.
The record lists no statistical analyses. It does not report confidence intervals, hypothesis tests, or an analysis of the primary endpoint. The code-generated tables and plots on this page can organize the posted observations, but they cannot fill in missing outcome details or overcome the design’s limited basis for comparison. The associated sample-size section is a planning illustration based on an observed effect, not a report of trial power or a feature of the original study design.
9. Statistical Methods Explained
The registry describes the study as Phase I, non-randomized, unmasked, and sequential. Those features matter for how the posted results can be interpreted. The design gives descriptive information about participants treated with the combination at different dose levels. It does not create a randomized comparison in which assignment balances participant characteristics across groups. The registry explicitly identifies the arms as not being a like-for-like control comparison.
What does a count endpoint show?
The primary outcome is a count of participants with grade 3 or higher adverse events related to study drug by Day 85. A count records the number of people meeting the event definition. It is not the same as a count of every event episode: one participant may experience more than one event, while the endpoint is framed around participants. The registry’s endpoint title states the dose levels of 140 mcg/kg and 100 mcg/kg, and its description refers to CTCAE v5.0 severity grading.
For a count to be interpreted fully, readers need the number assessed, the number meeting the endpoint, the event definition, and the relevant follow-up window. Here, the primary endpoint result by grade and dose is not reported in the registry record. The adverse-event summary provides at-risk and affected counts for serious and other adverse events, but it does not state that these are the primary grade 3-or-higher, study-drug-related counts. They should be read as distinct posted safety information rather than as a replacement endpoint result.
Why does the design limit comparisons?
Randomization is a general method for making treatment groups more comparable at the time of assignment. It does not guarantee identical groups, especially in small studies, but it supports a more defensible comparison than sequential, non-randomized assignment. In this study, the arms are dose escalation and dose expansion, and the registry says the study model was sequential. The record does not report the sequence or timing details needed to assess how participants entered each dose group.
With no random assignment, a difference between the groups could reflect dose, participant mix, timing, follow-up, or other factors. The record does not report an adjusted comparison that accounts for these possible influences. Even if the posted counts differ, they cannot be interpreted as evidence that one dose caused more or fewer events than the other. The small enrollment further limits the precision and generalizability of descriptive counts.
What does statistical uncertainty mean?
As general statistical context, uncertainty describes how much observed data may vary from the underlying pattern in a wider population. A confidence interval is one common way to express uncertainty around an estimate; it gives a range of values compatible with the data under specified assumptions. No confidence interval for the primary endpoint or the safety counts is reported in the registry record. Without such estimates, and with only a small enrolled group, the posted counts should not be mistaken for precise estimates of event frequency.
Over-dispersion is a general concern when event-count variability is greater than a model assumes. It is not a reported feature or analysis of this trial. Since the primary endpoint is a count of participants rather than a repeated-event rate, an over-dispersion model cannot be presumed appropriate. The statistical model, if any, for the original trial analyses is not reported in the registry record.
What do the planning calculations represent?
The sample-size section on this page is a planning illustration based on the observed effect, not the trial’s own design or an estimate of observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the calculation considers the effect to detect as a stated fraction of the observed effect. The displayed values are planning quantities, not additional participants observed in this study and not evidence that the study had a particular probability of detecting an effect.
General sample-size planning asks how many participants would be needed under chosen assumptions to detect a specified effect with a selected statistical criterion. Changing the assumed effect or analysis method can change the planning result. The registry does not report the original protocol’s sample-size justification or statistical plan, so the illustration must not be attributed to the investigators’ design choices.
Similarly, recalculations based on posted summary statistics, when present, are unadjusted calculations and do not replace the sponsor’s analysis. The record lists no analyses, and no sponsor analysis results for the primary endpoint are reported. The tables and plots should therefore be used to inspect the posted data descriptively, not to infer unreported adjusted effects, hypothesis tests, or causal conclusions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary safety endpoint and secondary outcomes that include partial or complete response, detectable LMB-100 in blood after Cycle 4, and serious and non-serious adverse events. It does not report a statistical plan describing how multiple outcomes were handled. Whether any multiplicity adjustment was planned or used is not reported in the registry record. Without that information, readers cannot tell whether a statistical claim across several outcomes was intended to control the chance of false-positive findings. The record lists no analyses, so it supplies no reported set of inferential results to assess for multiplicity.
Missing-data handling is also not reported in the registry record. The record does not state how participants who discontinued, missed assessments, or lacked Day 85 information were handled in the primary endpoint analysis. Nor does it report the analysis population definition or participant flow by outcome. Those details matter because a count depends on who was included and whether each participant was assessed during the stated period.
The primary endpoint’s reported population is not further specified in the available record. It is therefore unclear whether the analysis was intended to include all enrolled participants, only treated participants, or a different defined group. The registry’s overall enrollment and the safety at-risk counts do not settle that question. Any interpretation should remain limited to the counts explicitly posted, without assuming how unreported or unavailable observations were treated.
11. 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 |
|---|---|---|---|
| 140 mcg/kg LMB-100 + SEL-110 | 3 | 4 | 75.0% |
| 100 mcg/kg LMB-100 + SEL-110 | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 140 mcg/kg LMB-100 + SEL-110 | 2 of 4 |
| 100 mcg/kg LMB-100 + SEL-110 | 1 of 1 |
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 |
|---|---|
| 140 mcg/kg LMB-100 + SEL-110 | 3 of 4 |
| 100 mcg/kg LMB-100 + SEL-110 | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | 140 mcg/kg LMB-100 + SEL-110 | 100 mcg/kg LMB-100 + SEL-110 |
|---|---|---|---|
| Disease progression | General disorders | 2 of 4 | 0 of 1 |
| Lung infection | Infections and infestations | 0 of 4 | 1 of 1 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 0 of 4 | 1 of 1 |
| Atrial fibrillation | Cardiac disorders | 1 of 4 | 0 of 1 |
| Capillary leak syndrome | Vascular disorders | 1 of 4 | 0 of 1 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 4 | 0 of 1 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 4 | 0 of 1 |
| Infusion related reaction | Injury, poisoning and procedural complications | 1 of 4 | 0 of 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 4 | 0 of 1 |
| Non-cardiac chest pain | Musculoskeletal and connective tissue disorders | 1 of 4 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 140 mcg/kg LMB-100 + SEL-110 | 100 mcg/kg LMB-100 + SEL-110 |
|---|---|---|---|
| Hyponatremia | Metabolism and nutrition disorders | 3 of 4 | 1 of 1 |
| Lymphocyte count decreased | Investigations | 3 of 4 | 1 of 1 |
| Anemia | Blood and lymphatic system disorders | 2 of 4 | 1 of 1 |
| Aspartate aminotransferase increased | Investigations | 3 of 4 | 0 of 1 |
| Constipation | Gastrointestinal disorders | 2 of 4 | 1 of 1 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 4 | 1 of 1 |
| Edema limbs | General disorders | 2 of 4 | 1 of 1 |
| Hyperkalemia | Metabolism and nutrition disorders | 2 of 4 | 1 of 1 |
| Hypermagnesemia | Metabolism and nutrition disorders | 3 of 4 | 0 of 1 |
| Hypokalemia | Metabolism and nutrition disorders | 2 of 4 | 1 of 1 |
Serious events with the highest arm-level rate: lung infection (100.0%), pneumonitis (100.0%), disease progression (50.0%), atrial fibrillation (25.0%), capillary leak syndrome (25.0%).
The posted safety summary lists serious adverse-event affected counts of 3 among 4 at risk in the 140 mcg/kg LMB-100 + SEL-110 group, and 1 among 1 at risk in the 100 mcg/kg group. For other adverse events, it lists 3 among 4 at risk in the 140 mcg/kg group and 1 among 1 at risk in the 100 mcg/kg group. These are participant counts in the registry summary; they do not identify severity, relatedness, timing, or the number of individual event episodes for every affected participant.
The primary endpoint is narrower: grade 3 or higher events related to study drug at Day 85. The safety figures above do not report that endpoint’s grade- and dose-specific counts. The registry also lists deaths of 2 and 1 in the respective groups, but the cause and relationship to treatment are not reported in this summary. Those deaths should not be assumed to be treatment-related.
The serious-event term list gives percentages for lung infection, pneumonitis, disease progression, atrial fibrillation, capillary leak syndrome, and dyspnea. The denominator and counting rules behind those percentages are not reported in the registry record. Given the small enrollment and non-randomized sequential design, these entries describe the record’s observed safety data rather than comparative risks or estimates for a wider population.
12. What the Result Does, and Does Not, Mean
This trial record describes a small, sequential Phase I study of LMB-100 plus SEL-110 in people with mesothelioma. It reports safety counts for two dose groups and identifies a primary endpoint focused on grade 3 or higher study-drug-related adverse events by Day 85. The posted counts provide a descriptive account of adverse events recorded among participants at risk in the respective groups.
The record does not report the primary endpoint result by grade and dose, statistical analyses, confidence intervals, or a detailed assessment of the listed deaths. It also does not report results for the listed secondary outcomes in the information. As a result, the record does not support a conclusion about the comparative effect of the two dose levels, the frequency of events in a broader population, or a causal relationship between treatment and each listed event.
The non-randomized design is especially important. The dose groups were not randomized controls, and sequential assignment can leave groups different for reasons other than dose. With 5 participants enrolled overall, even descriptive counts provide limited information about how stable an event pattern might be in a larger group. A count observed in this study should not be read as a precise rate for other patients or settings.
The registry status is terminated, but the reason is not reported in the registry record. Termination alone does not explain whether the study stopped for safety, recruitment, operational, or other reasons. The record also does not report the protocol’s sample-size justification, interim analyses, or original statistical plan. Those absences limit interpretation and should not be filled by assumptions.
In short, the posted data document safety observations from this study, but they do not establish a treatment benefit or lack of benefit, nor do they establish a comparative safety conclusion. The tables, plots, and planning calculations can help organize or illustrate the available information; they cannot substitute for unreported endpoint results or analyses.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the limits of early-phase safety data. Its stated purpose was to assess the safety and tolerability of LMB-100 with SEL-110 in advanced mesothelioma, while the primary endpoint counted grade 3 or higher adverse events related to study drug at Day 85. That endpoint definition makes clear why event severity, timing, and attribution are essential to interpretation, not just the presence of any adverse event.
The record also illustrates why design labels matter. Dose escalation and dose expansion are sequential, non-randomized groups, not interchangeable treatment arms in a controlled comparison. Even when event counts are displayed side by side, the design does not establish that differences are caused by dose. This distinction is particularly important when enrollment is 5 and the safety groups have small at-risk counts.
Finally, the record shows the importance of separating observed safety summaries from the primary endpoint and from statistical inference. Serious and other adverse-event counts are useful descriptions, but the grade-specific, study-drug-related primary endpoint result is not reported in the registry record. No analyses are listed. Statistical transparency includes stating what is known, what was analyzed, and what remains unavailable; here, the missing details constrain the conclusions that readers can draw.
14. 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 limitations specific to this record constrain interpretation. Enrollment was 5, and the safety at-risk counts were 4 in the 140 mcg/kg group and 1 in the 100 mcg/kg group. Counts from groups this small provide limited precision and cannot establish how frequently events would occur in a wider population. The registry does not report the participant characteristics needed to assess how representative the enrolled group was.
The study was non-randomized, unmasked, and sequential. The dose groups therefore are not like-for-like controls, and the record reports no adjusted analysis to address potential differences between them. The reason for termination is not reported. Participant flow, discontinuations, and follow-up completeness are also not reported in the registry record.
The registry identifies a primary endpoint of grade 3 or higher study-drug-related adverse events by Day 85, but does not report its counts by dose and grade. The safety summary does not provide enough detail to reconstruct that endpoint. The cause and treatment relationship of the deaths are not reported in the summary, and the denominators for the listed serious-event percentages are not stated.
Finally, the statistical analysis plan, missing-data approach, analysis populations, multiplicity handling, interim analyses, and protocol sample-size justification are not reported in the registry record. The planning illustration is not the original trial design and is not observed power. These gaps preclude strong comparative or inferential conclusions from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma — NCT03436732.
- Registry record last updated 2019-11-22; status last verified 2019-11.
- Results first posted 2019-11-22.
- 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.
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18. Record Summary
The registry record describes a Phase I, non-randomized, unmasked, sequential study of LMB-100 plus SEL-110 in malignant pleural or peritoneal mesothelioma. Enrollment was 5; the study status is terminated. The recorded study start was 2018-02-28, and primary completion was 2019-04-30. The registry describes dose escalation and dose expansion rather than randomized treatment groups.
The primary endpoint was the number of participants with grade 3 or higher adverse events related to study drug at dose levels 140 mcg/kg and 100 mcg/kg, assessed at Day 85. The posted safety summary lists serious and other adverse-event counts and deaths by dose group. The primary endpoint result by grade and dose, the reason for termination, and statistical analyses are not reported in the registry record.